ADIPOQ

This gene is expressed in adipose tissue exclusively. It encodes a protein with similarity to collagens
X and VIII and complement factor C1q. The encoded protein circulates in the plasma and is involved
with metabolic and hormonal processes. Mutations in this gene are associated with adiponectin
deficiency. Multiple alternatively spliced variants, encoding the same protein, have been identified.
[provided by RefSeq, Apr 2010]

Role in Inflammation

Its role in inflammation is controversial, as its plasma concentration decreases in diseases such as
metabolic syndrome and type II diabetes [11], but increases in some inflammatory diseases such as
rheumatoid arthritis and systemic lupus erythematosus [.

CD247
The protein encoded by this gene is T-cell receptor zeta, which together with T-cell receptor
alpha/beta and gamma/delta heterodimers, and with CD3-gamma, -delta and -epsilon, forms the T-
cell receptor-CD3 complex. The zeta chain plays an important role in coupling antigen recognition to
several intracellular signal-transduction pathways. Low expression of the antigen results in impaired
immune response. Two alternatively spliced transcript variants encoding distinct isoforms have been
found for this gene. [provided by RefSeq, Jul 2008]

CD247, which encodes the CD3 ζ chain, is involved in the assembly and expression of the T-cell
receptor complex and in signal transduction on antigen triggering
Role in Inflammation

genome-wide association studies have demonstrated an association of variants in CD247 with

systemic sclerosis, rheumatoid arthritis, and other autoimmune-related disorders.

ur study adds four novel loci to established RA and CD risk loci (CD247, UBE2L3, DDX6,
and UBASH3A). It also adds four loci previously established in one or the other disease to the list of
shared CD-RA risk loci (SH2B3, 8q24.2, STAT4, and TRAF1-C5). With six previously established CD-RA
risk loci, there are now 14 shared CD-RA risk loci

Epidemiology and candidate gene studies indicate a shared genetic basis for celiac disease (CD) and
rheumatoid arthritis (RA)
HSPA1B

This intronless gene encodes a 70kDa heat shock protein which is a member of the heat shock
protein 70 family. In conjuction with other heat shock proteins, this protein stabilizes existing proteins
against aggregation and mediates the folding of newly translated proteins in the cytosol and in
organelles. It is also involved in the ubiquitin-proteasome pathway through interaction with the AU-rich
element RNA-binding protein 1. The gene is located in the major histocompatibility complex class III
region, in a cluster with two closely related genes which encode similar proteins. [provided by RefSeq,
Jul 2008]

Role in Inflammation

gene expression regulation shows that the HSPA1B is an – on HLA-DRB1 –

independent molecular marker for myositis development
The expression of both, the HSPA1A and HSPA1B genes was significantly
upregulated (p<0.001; p<0.05) in patients suffering from myositis when
compared to controls
IRAK2

IRAK2 encodes the interleukin-1 receptor-associated kinase 2, one of two putative serine/threonine
kinases that become associated with the interleukin-1 receptor (IL1R) upon stimulation. IRAK2 is
reported to participate in the IL1-induced upregulation of NF-kappaB. [provided by RefSeq, Jul 2008]

Role in Inflammation

IRAK-2 possesses catalytic activity and has been implicated in maintenance of pro-inflammatory
cytokine release induced by TLR4 and TLR9 engagement. The role of IRAK-2 as a regulator of TLR
signaling may be more complex than originally thought. IRAK-2 is known to induce NF-κB activation
through TLR3, TLR4, and TLR8 (14). Of note, IRAK-2 is the only member of the family thought to
mediate signaling through TLR3. Interestingly, IRAK-2 has recently been shown to have a dual
function (immunosuppressive and immunostimulatory) in TLR9 related signaling and inflammatory
responses. Wan and colleagues demonstrated that IRAK-2 suppresses TLR9 signaling in the early
post-stimulation phase, raising the activation threshold for TLR9-induced inflammatory response and
potentially preventing autoimmunity (36). However, if the higher activation threshold is successfully
triggered through a strong stimulus, IRAK-2 mediates a positive feedback loop allowing for sustained
release of pro-inflammatory cytokines. It is conceivable that loss of negative regulatory function
could allow sustained IRAK-2 activation and inflammation, thus, promoting carcinogenesis.

RIPK2
This gene encodes a member of the receptor-interacting protein (RIP) family of serine/threonine
protein kinases. The encoded protein contains a C-terminal caspase activation and recruitment
domain (CARD), and is a component of signaling complexes in both the innate and adaptive immune
pathways. It is a potent activator of NF-kappaB and inducer of apoptosis in response to various
stimuli. [provided by RefSeq, Jul 2008]

Role in Inflammation
The RIPK2 kinase transduces signaling downstream of the intracellular peptidoglycan sensors NOD1 and NOD2 to
promote a productive inflammatory response. . Crohn’s disease-associated mutations that abrogate NOD2
binding to MDP may induce excessive inflammatory signaling from other pattern recognition
receptors, including NOD1 (Couturier-Maillard et al., 2013; Inohara et al., 2003). In contrast,
mutations in the second major Crohn’s disease susceptibility factor, ATG16L1, disrupt an inhibitory
interaction with NOD2 and consequently increase the activation of RIPK2 (Sorbara et al., 2013).
Excessive RIPK2 activation has also been reported in pediatric Crohn’s disease (Negroni et al., 2009).
In addition, gain of function in the NOD2-RIPK2 pathway has been linked to Blau syndrome, early-
onset sarcoidosis, allergic airway inflammation, and multiple sclerosis (Goh et al., 2013; Jun et al.,
2013; Shaw et al., 2011).

TBP
Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides.
The protein that coordinates these activities is transcription factor IID (TFIID), which binds to the core
promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of
the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the
TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-
associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators,
function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex
assembly and transcription initiation. This gene encodes TBP, the TATA-binding protein. A distinctive
feature of TBP is a long string of glutamines in the N-terminus. This region of the protein modulates
the DNA binding activity of the C terminus, and modulation of DNA binding affects the rate of
transcription complex formation and initiation of transcription. The number of CAG repeats encoding
the polyglutamine tract is usually 25-42, and expansion of the number of repeats to 45-66 increases
the length of the polyglutamine string and is associated with spinocerebellar ataxia 17, a
neurodegenerative disorder classified as a polyglutamine disease. Two transcript variants encoding
different isoforms have been found for this gene. [provided by RefSeq, Jul 2016]

Role in Inflammation

TBP blocks expression of TNF-induced transcripts involved in inflammation and

invasion.

ALOX5AP

This gene encodes a protein which, with 5-lipoxygenase, is required for leukotriene synthesis.
Leukotrienes are arachidonic acid metabolites which have been implicated in various types of
inflammatory responses, including asthma, arthritis and psoriasis. This protein localizes to the plasma
membrane. Inhibitors of its function impede translocation of 5-lipoxygenase from the cytoplasm to the
cell membrane and inhibit 5-lipoxygenase activation. Alternatively spliced transcript variants encoding
different isoforms have been identified for this gene. [provided by RefSeq, Feb 2011]

Role in Inflammation

The ALOX5AP gene is required for the synthesis of leukotrienes, a protein family involved in
inflammatory responses.

CD3D

The protein encoded by this gene is part of the T-cell receptor/CD3 complex (TCR/CD3 complex) and
is involved in T-cell development and signal transduction. The encoded membrane protein represents
the delta subunit of the CD3 complex, and along with four other CD3 subunits, binds either TCR
alpha/beta or TCR gamma/delta to form the TCR/CD3 complex on the surface of T-cells. Defects in
this gene are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-
cell-positive/NK-cell-positive (SCIDBNK). Two transcript variants encoding different isoforms have
been found for this gene. Other variants may also exist, but the full-length natures of their transcripts
has yet to be defined. [provided by RefSeq, Feb 2009]

Role in Inflammation
DECLINE IN EXPRESSION OF NK CELL– AND T CELL–DERIVED
GENESNK cells and T cells participate in the eradication of invading bacteria, not only by interacting with
monocytes
but also via direct mechanisms (19 ). Hence, a reduced activity or a reduction in the number of circulating
NK cells and T cells could lead to an impaired defense against microorganisms. mRNA production
by T cell–associated genes, including CD3D, CCR3, and CD69, and by NK cell–associated genes (KLRD1,
KLRK1, and PRF1) shows similar time courses, with highly significant decreases in mRNA production ap-
parent between the preoperative and postoperative time points in both investigated groups (Table
2). This observation suggests a general effect of surgical intervention on the 2 groups, a finding
consistent with published studies(4, 20 ). We found decreased mRNA production in the sepsis group
for CD3D, PRF1, KLRD1, and KLRK1 but noted no such differences for the remaining genes.
the decreased expression of such genes as CD3D and PRF1 in T cells and NK cells in patients who
developed sepsis in our study suggests a pivotal role of cell-mediated immunity in the risk for
postoperative sepsis
IL17A
The protein encoded by this gene is a proinflammatory cytokine produced by activated T cells. This
cytokine regulates the activities of NF-kappaB and mitogen-activated protein kinases. This cytokine
can stimulate the expression of IL6 and cyclooxygenase-2 (PTGS2/COX-2), as well as enhance the
production of nitric oxide (NO). High levels of this cytokine are associated with several chronic
inflammatory diseases including rheumatoid arthritis, psoriasis and multiple sclerosis. [provided by
RefSeq, Jul 2008]

Role in Inflammation
dysregulated IL-17A and IL-17F production can result in excessive pro-inflammatory cytokine
expression and chronic inflammation, which lead to tissue damage and autoimmunity. IL-17A is
readily detected in the synovial fluids and synovium of RA patients.46 Several studies using mouse
models of RA have demonstrated a key role for IL-17A in the progression of disease IL-17A mainly
mediates its immune regulatory function by promoting the generation of pro-inflammatory
cytokines and chemokines, which leads to the attraction of neutrophils and macrophages to the
inflammation site. The receptor for IL-17A is widely expressed among non-haematopoietic cells, such
as fibroblasts and epithelial cells, and among innate immune cells, such as macrophages and
neutrophils. The treatment of fibroblasts with IL-17A results in the upregulation of several cytokines,
including chemokine (C–X–C motif) ligand 1 (CXCL1), chemokine (C–C motif) ligand 2 (CCL2), CCL7,
CCL20 and matrix metalloproteinase 3 IL-17 has been correlated to a growing number of
autoimmune and inflammatory diseases such as rheumatoid arthritis, psoriasis, asthma, and IBD..

MAGEA2 Gene
This gene is a member of the MAGEA gene family. The members of this family encode proteins with
50 to 80% sequence identity to each other. The promoters and first exons of the MAGEA genes show
considerable variability, suggesting that the existence of this gene family enables the same function to
be expressed under different transcriptional controls. The MAGEA genes are clustered at
chromosomal location Xq28. They have been implicated in some hereditary disorders, such as
dyskeratosis congenita. This gene has two identical copies at different loci. Alternatively spliced
transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq,
Jul 2008]

Role in Inflammation
In human fibroblasts, Mage-A2 was found to maintain cell proliferation in response to RasV12 expression
by limiting the senescence response to this oncogene [65]. This effect of Mage-A2 was also attributed to
its inhibition of p53 function, suggesting that MAGE-A2 could play a novel role in early progression to
malignancy by interfering with p53 function. This may block the senescence program, a critical barrier
against cell transformation.
In the samples derived from patients with acute sigma diverticulitis specimen we found one
sample being positive for MAGE-A1, MAGE-A2, RAGE-4 and cTAGE-1, and a second specimen
positive for NY-ESO-1.
MageA2/HDAC3 is a p53-repressing complex, where the tumor antigen MageA2 acts as p53–
HDAC3 assembling protein, giving survival advantage to cells treated with DNA-damaging
agents. MAGEA2 is growth promoting, in part, through its interaction with the p53 pathway by
increasing cellular proliferation and decreasing cell cycle arrest. suppression of MAGEA2 in
lung cancer cells significantly reduced the growth/survival of cancer cells.

RORC gene

The protein encoded by this gene is a DNA-binding transcription factor and is a member of the NR1
subfamily of nuclear hormone receptors. The specific functions of this protein are not known;
however, studies of a similar gene in mice have shown that this gene may be essential for lymphoid
organogenesis and may play an important regulatory role in thymopoiesis. In addition, studies in mice
suggest that the protein encoded by this gene may inhibit the expression of Fas ligand and IL2. Two
transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq,
Jul 2008]

Role in Inflammation

Retinoic-acid-orphan-receptor-C (RORC) is a master regulator of Th17 cells, which are pathogenic in

several autoimmune diseases. Genetic Rorc deficiency in mice, while preventing autoimmunity,
causes early lethality due to metastatic thymic T cell lymphomas.

BAX Gene

The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form
hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety
of cellular activities. This protein forms a heterodimer with BCL2, and functions as an apoptotic
activator. This protein is reported to interact with, and increase the opening of, the mitochondrial
voltage-dependent anion channel (VDAC), which leads to the loss in membrane potential and the
release of cytochrome c. The expression of this gene is regulated by the tumor suppressor P53 and
has been shown to be involved in P53-mediated apoptosis. Multiple alternatively spliced transcript
variants, which encode different isoforms, have been reported for this gene. [provided by RefSeq, Jul
2008]

Role in Inflammation
Tregs play an important role in controlling the pathogenesis of inflammatory atherosclerosis(3, 4). In
addition, IL-2 knock-out mice have a deficiency in Tregs, and spontaneously develop autoimmune
diseases including vasculitis(12). However, it remains to be determined if a deficiency in Treg
generation in IL-2 knock-out mice, or higher susceptibility of Tregs to apoptosis induced by IL-2
deficiency, contributes to accelerated vasculitis. Since Tregs with high affinity IL-2 receptor have
higher susceptibility to apoptosis in comparison to CD4+CD25− T cells, characterization of IL-2
withdrawal-Bax pathway in Tregs would be important in generating a substantial quantity of well-
survived Tregs for Treg-based immune therapeutics(13

higher expression of Bax in Tregs decreases the striking threshold of vascular inflammation due to
promotion of Treg apoptosis and presumably failure in suppressing anti-vascular immune cell
clones. igher expression of Bax in transgenic Tregs “amplifies” cuff-induced vascular inflammation.

CD74
The protein encoded by this gene associates with class II major histocompatibility complex (MHC)
and is an important chaperone that regulates antigen presentation for immune response. It also
serves as cell surface receptor for the cytokine macrophage migration inhibitory factor (MIF) which,
when bound to the encoded protein, initiates survival pathways and cell proliferation. This protein also
interacts with amyloid precursor protein (APP) and suppresses the production of amyloid beta
(Abeta). Multiple alternatively spliced transcript variants encoding different isoforms have been
identified. [provided by RefSeq, Aug 2011]

Role in Inflammation
Some studies also suggest that CD74 might be expressed independently of class II MHC, indicating
additional functions[2]. Various studies have indicated that CD74 is highly expressed in inflammatory
disorders and cancers. It also acts as a receptor for macrophage migration inhibitory factor (MIF) and
facilitates adhesion of Helicobacter pylori (H pylori) to gastric epithelial cells (GECs)[3,4]. CD74
expression is increased during H pylori infection, chronic inflammatory conditions of the
gastrointestinal (GI) tract, and gastric and colon cancers. One critical function it has in carcinogenesis
is to act as an accessory signaling molecule for cell proliferation.

IL18 Gene
The protein encoded by this gene is a proinflammatory cytokine that augments natural killer cell
activity in spleen cells, and stimulates interferon gamma production in T-helper type I cells.
Alternatively spliced transcript variants encoding different isoforms have been found for this
gene.[provided by RefSeq, Aug 2011]

Role in inflammation

Interleukin-18 exhibits characteristics of other pro-inflammatory cytokines,

such as increases in cell adhesion molecules, nitric oxide synthesis, and
chemokine production. Because IL-18 can increase IFNγ production,
blocking IL-18 activity in autoimmune diseases is an attractive therapeutic
target since anti-IL-12/23 reduces the severity of Crohn’s disease as well as
psoriasis.

Blocking IL-18 with the IL-18 binding protein (IL-18BP) (see Figure 1) also
reduces colitis induced by antigen sensitization (45). Since generation of
active IL-18 requires caspase-1, studies have also been performed in mice
deficient in caspase-1 and subjected to DSS colitis . Administration of
exogenous IL-18 restored mucosal healing in caspase-1-deficient mice (52).
Also, mice deficient in NLRP3 were more susceptible to either DSS or
TNBS-induced colitis and exhibited decreased IL-1β as well as decreased
beta-defensins (53). Macrophages from NLRP3-deficient mice failed to
respond to MDP (53). Mice deficient in NLRP6 are also more vulnerable to
DSS (54, 55) and the susceptibility appears to be due to lack of sufficient IL-
18.

NFKB1 Gene

This gene encodes a 105 kD protein which can undergo cotranslational processing by the 26S
proteasome to produce a 50 kD protein. The 105 kD protein is a Rel protein-specific transcription
inhibitor and the 50 kD protein is a DNA binding subunit of the NF-kappa-B (NFKB) protein complex.
NFKB is a transcription regulator that is activated by various intra- and extra-cellular stimuli such as
cytokines, oxidant-free radicals, ultraviolet irradiation, and bacterial or viral products. Activated NFKB
translocates into the nucleus and stimulates the expression of genes involved in a wide variety of
biological functions. Inappropriate activation of NFKB has been associated with a number of
inflammatory diseases while persistent inhibition of NFKB leads to inappropriate immune cell
development or delayed cell growth. Alternative splicing results in multiple transcript variants
encoding different isoforms, at least one of which is proteolytically processed. [provided by RefSeq,
Feb 2016]

Role in inflammation

The transcription factor NF-κB regulates multiple aspects of innate and adaptive immune functions
and serves as a pivotal mediator of inflammatory responses. NF-κB induces the expression of various
pro-inflammatory genes, including those encoding cytokines and chemokines, and also participates
in inflammasome regulation. In addition, NF-κB plays a critical role in regulating the survival,
activation and differentiation of innate immune cells and inflammatory T cells.

The nuclear factor NF-κB pathway has long been considered a prototypical proinflammatory
signaling pathway, largely based on the role of NF-κB in the expression of proinflammatory genes
including cytokines, chemokines, and adhesion molecules. In this article, we describe how genetic
evidence in mice has revealed complex roles for the NF-κB in inflammation that suggest both pro-
and anti-inflammatory roles for this pathway.
Nfkb1(-/-) mice display increased inflammation and susceptibility to certain forms of DNA damage,
leading to cancer, and a rapid ageing phenotype

S100A8 Gene

The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand
calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of
cells, and involved in the regulation of a number of cellular processes such as cell cycle progression
and differentiation. S100 genes include at least 13 members which are located as a cluster on
chromosome 1q21. This protein may function in the inhibition of casein kinase and as a cytokine.
Altered expression of this protein is associated with the disease cystic fibrosis. Multiple transcript
variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

Role in inflammation
The specific function and disease relevance of calgranulin genes is complex. Expression and protein
levels are increased during immune activation and inflammation, in diverse disease settings including
diabetes, obesity, cardiovascular disease, arthritis, cancer, pancreatitis, psoriasis, inflammatory bowel
disease, and pathogenic infection.[9–14] Serum S100A12 associates with risk of CAD in subjects with
T2DM.[15

BCL2 Gene

This gene encodes an integral outer mitochondrial membrane protein that blocks the apoptotic death
of some cells such as lymphocytes. Constitutive expression of BCL2, such as in the case of
translocation of BCL2 to Ig heavy chain locus, is thought to be the cause of follicular lymphoma.
Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

Role in inflammation

expression of Bcl-2, a cell survival protein that plays a role in apoptosis by blocking programmed cell
death (24), and the expression of proliferating cell nuclear antigen (PCNA), a proliferation marker
(25). The results suggest an inverse correlation between the expression of Bcl-2 and that of PCNA in
epithelial cells under the influence of chronic inflammation. Bcl-2 in monocytes since over-
expression of Bcl-2 in monocytic cell lineages has been shown to protect monocytes from apoptosis.
Damage to the Bcl-2 gene has been identified as a cause of a number of cancers,
including melanoma, breast, prostate, chronic lymphocytic leukemia, and lung cancer, and a
possible cause of schizophrenia and autoimmunity. It is also a cause of resistance to cancer
treatments
DEFA6 Gene

Defensins are a family of antimicrobial and cytotoxic peptides thought to be involved in host defense.
They are abundant in the granules of neutrophils and also found in the epithelia of mucosal surfaces
such as those of the intestine, respiratory tract, urinary tract, and vagina. Members of the defensin
family are highly similar in protein sequence and distinguished by a conserved cysteine motif. Several
alpha defensin genes appear to be clustered on chromosome 8. The protein encoded by this gene,
defensin, alpha 6, is highly expressed in the secretory granules of Paneth cells of the small intestine,
and likely plays a role in host defense of human bowel. [provided by RefSeq, Oct 2014]

Role in inflammation
atients with Crohn's ileitis (CDi) show a reduced antibacterial activity in their intestinal mucosal
extracts and display a decreased expression of the Paneth cell alpha-defensins
(DEFA5 and DEFA6) marked upregulation of DEFA5 and DEFA6 expression in inflamed UC colon

IL-1β Gene
Role in inflammation

IL-1β is a pro-inflammatory cytokine that has been implicated in pain, inflammation and
autoimmune conditionsoverproduction of IL-1β is implicated in the pathophysiological changes that
occur during different disease states, such as rheumatoid arthritis, neuropathic pain, inflammatory
bowel disease, osteoarthritis, vascular disease, multiple sclerosis, and Alzheimer's disease
NFKBIA gene
This gene encodes a member of the NF-kappa-B inhibitor family, which contain multiple ankrin repeat
domains. The encoded protein interacts with REL dimers to inhibit NF-kappa-B/REL complexes which
are involved in inflammatory responses. The encoded protein moves between the cytoplasm and the
nucleus via a nuclear localization signal and CRM1-mediated nuclear export. Mutations in this gene
have been found in ectodermal dysplasia anhidrotic with T-cell immunodeficiency autosomal
dominant disease. [provided by RefSeq, Aug 2011]

Role in inflammation

unctioning as a candidate tumor suppressor gene involved in controlling the oncogenic potential
of NF-kB, nuclear factor-kappa-B inhibitor-alpha (NFKBIA) precludes nuclear translocation, DNA
binding, and phosphorylation by protein kinase alpha.14 The highly polymorphic NFKBIA gene at
chromosome 14q13 spanning approximately 3.5 kb consists of 6 exons. Single nucleotide
polymorphisms (SNPs) in the promoter region of NFKBIA are reported to be associated with the
initiations of breast cancer, colorectal cancer, Hodgkin lymphoma, multiple myeloma, and
melanomagenetic variation in the promoter region of NFKBIA has been linked to alterations in
susceptibility to infectious and inflammatory diseases, as well as a variety of cancers . genetic variants in
the promoter of NFKBIA (rs3138053, rs2233406, and rs2233409) influence NFKBIA promoter function,
gene and IκBα protein expression, and TLR-mediated inflammatory responses

S100A9 gene
The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand
calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of
cells, and involved in the regulation of a number of cellular processes such as cell cycle progression
and differentiation. S100 genes include at least 13 members which are located as a cluster on
chromosome 1q21. This protein may function in the inhibition of casein kinase and altered expression
of this protein is associated with the disease cystic fibrosis. This antimicrobial protein exhibits
antifungal and antibacterial activity. [provided by RefSeq, Nov 2014]

Role in inflammation

. S100A8 and S100A9 are low molecular weight calcium binding proteins and are found at high levels
in the extracellular milieu during inflammatory condition. S100A8/A9 also exhibits cytokine-like
functions enhancing leukocyte recruitment to inflammatory sites [
BIRC5 Gene

 This gene is a member of the inhibitor of apoptosis (IAP) gene family, which encode negative
regulatory proteins that prevent apoptotic cell death. IAP family members usually contain
multiple baculovirus IAP repeat (BIR) domains, but this gene encodes proteins with only a
single BIR domain. The encoded proteins also lack a C-terminus RING finger domain.
Gene expression is high during fetal development and in most tumors, yet low in adult
tissues. Alternatively spliced transcript variants encoding distinct isoforms have been found
for this gene. [provided by RefSeq, Jun 2011]

 Role in inflammation

Baculoviral IAP repeat containing 5 (BIRC5) (also known as survivin) is an important member of
the inhibitor of apoptosis protein family. Its impact in blocking apoptosis has already been
widely demonstrated in the literature. However, it has been extensively demonstrated that
during tumorigenesis, survivin is dramatically over-expressed and therefore has been identified
as a candidate target for cancer therapy . Strikingly, neutrophil hematopoietic growth factors
reactivated the survivin gene in these terminally differentiated cells, which are unable to resume
cell cycle progression at G2-M, and high levels of survivin were expressed in mature neutrophils
under inflammatory conditions in vivo
FOXP3 Gene

The protein encoded by this gene is a member of the forkhead/winged-helix family of transcriptional
regulators. Defects in this gene are the cause of immunodeficiency polyendocrinopathy, enteropathy,
X-linked syndrome (IPEX), also known as X-linked autoimmunity-immunodeficiency syndrome.
Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by
RefSeq, Jul 2008]

Role in inflammation

majority of FOXP3 gene targets in CD4+ lymphocytes isolated from Crohn’s lesions are
significantly up-regulated. Moreover, FoxP3 is an important tumor suppressor gene in carcinomas
and has putative cancer suppressor gene function in cutaneous melanoma as well. Foxp3 is the
master regulator of the Treg gene expression program, and consequently Foxp3 mutation in both
humans and mice is sufficient to trigger the development of severe lymphoproliferative
autoimmune disorders (18⇓⇓⇓⇓⇓–24). Foxp3 is essential both for driving natural Treg (nTreg)
development within the thymus and for maintaining lineage identity and suppressive function of
peripheral Tregs: Deletion of Foxp3 specifically in postthymic mature Tregs completely abolishes
their ability to suppress the onset of effector T-cell–mediated autoimmunity

IL23A

This gene encodes a subunit of the heterodimeric cytokine interleukin 23 (IL23). IL23 is composed of
this protein and the p40 subunit of interleukin 12 (IL12B). The receptor of IL23 is formed by the beta 1
subunit of IL12 (IL12RB1) and an IL23 specific subunit, IL23R. Both IL23 and IL12 can activate the
transcription activator STAT4, and stimulate the production of interferon-gamma (IFNG). In contrast to
IL12, which acts mainly on naive CD4(+) T cells, IL23 preferentially acts on memory CD4(+) T cells.
[provided by RefSeq, Jul 2008]
Role in inflammation

IL23A mediates its known biological functions by dimerizing with IL12B to form IL-23, which
is a potent proinflammatory cytokine essential for the functions of the IL-17-producing T
helper cells (Th17) (Langrish et al., 2005). Reminiscent of the IKKβ knockout
mouse phenotype, while IL23A null mice were protected against infection-induced
inflammation, they succumbed to infection due to defective clearance, hence demonstrating
a protective function for IL23A (Mangan et al., 2006)
NFKBIZ Gene

This gene is a member of the ankyrin-repeat family and is induced by lipopolysaccharide (LPS). The
C-terminal portion of the encoded product which contains the ankyrin repeats, shares high sequence
similarity with the I kappa B family of proteins. The latter are known to play a role in inflammatory
responses to LPS by their interaction with NF-B proteins through ankyrin-repeat domains. Studies in
mouse indicate that this gene product is one of the nuclear I kappa B proteins and an activator of IL-6
production. Two transcript variants encoding different isoforms have been found for this gene.
[provided by RefSeq, Jul 2008]

Role in inflammation

IκB-ζ, encoded by the Nfkbiz gene, is a member of the nuclear IκB family of proteins that
acts as a transcriptional regulator via association with NF-κB (Yamazaki et al., 2001). L IκB-
ζ-deficient mice spontaneously develop severe inflammation in the conjunctiva and
periocular skin. IκBζ is mostly regarded as a pro-inflammatory regulator, as demonstrated e.g. by its requirement
for Th17 differentiation and expression of particular pro-inflammatory cytokines. Nevertheless, Nfkbiz−/− mice show a
pro-inflammatory phenotype and M1 hyperpolarization of macrophages (15, 16, 24, 25), suggesting that so far
unknown anti-inflammatory mediators might be controlled by IκBζ. The enhanced expression of IL-17 that is
observed in patients with Crohn's disease could act on intestinal fibroblasts to induce expression of
transcription factor NFKBIZ and proinflammatory chemokine CXCL1. This can have consequences for
fibroblast activity and neutrophil chemotaxis. In patients with ulcerative colitis, the expression of
lipocalin-2, an essential marker of activity of the disease, is regulated synergically by IL17-A, IL22 and
TNFα in an IκBζ-dependent manner
TGFB1

This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of
proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation
of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is
proteolytically processed to generate a latency-associated peptide (LAP) and a mature peptide, and is
found in either a latent form composed of a mature peptide homodimer, a LAP homodimer, and a
latent TGF-beta binding protein, or in an active form consisting solely of the mature peptide
homodimer. The mature peptide may also form heterodimers with other TGFB family members. This
encoded protein regulates cell proliferation, differentiation and growth, and can modulate expression
and activation of other growth factors including interferon gamma and tumor necrosis factor alpha.
This gene is frequently upregulated in tumor cells, and mutations in this gene result in Camurati-
Engelmann disease. [provided by RefSeq, Aug 2016]

Role in inflammation

TGFβ1 is a very potent stimulator of chemotaxis; TGFβ1 stimulates migration of

monocytes, lymphocytes, neutrophils and fibroblasts with 10-15 M concentrations [2].
There are several animal models study the effects of TGFβ1. TGFβ1 knockout mice die
from multifocal inflammation and autoimmune disorders in internal organs, suggesting
its immune suppressive effect in these organs [3, 4]. However, TGFβ1 knockout mice
lack Langerhans cells, which require TGFβ1 for development and activation, and
therefore do not have skin inflammation [5, 6]. Furthermore, overexpression of TGFβ1 in
the epidermis of K5.TGFβ1 mice (latent human TGFβ1 overexpression targeted to
epidermal keratinocytes by keratin 5) results in significant skin inflammation [7],
whereas their internal organs are protected from inflammation and autoimmune diseases
by elevated systemic levels of TGFβ1 secreted by K5.TGFβ1 keratinocytes . LPMC isolated
from CD patients produced significantly less TGF-β1 than controls when stimulated via CD2 plus
CD28 pathways (P = 0·001)] conversely, in UC patients increased production of TGF-β1 compared to
controls was observed (P = 0·0005).
CALCA Gene

This gene encodes the peptide hormones calcitonin, calcitonin gene-related peptide and katacalcin by
tissue-specific alternative RNA splicing of the gene transcripts and cleavage of inactive precursor
proteins. Calcitonin is involved in calcium regulation and acts to regulate phosphorus metabolism.
Calcitonin gene-related peptide functions as a vasodilator and as an antimicrobial peptide while
katacalcin is a calcium-lowering peptide. Multiple transcript variants encoding different isoforms have
been found for this gene.[provided by RefSeq, Aug 2014]

Role in inflammation

Calcitonin gene–related peptide (CGRP; official name CALCA) has a variety of functions and
exhibits both angiogenic and anti-inflammatory properties
HLA-DRA

HLA-DRA is one of the HLA class II alpha chain paralogues. This class II molecule is a heterodimer
consisting of an alpha and a beta chain, both anchored in the membrane. It plays a central role in the
immune system by presenting peptides derived from extracellular proteins. Class II molecules are
expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The alpha
chain is approximately 33-35 kDa and its gene contains 5 exons. Exon 1 encodes the leader peptide,
exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane
domain and the cytoplasmic tail. DRA does not have polymorphisms in the peptide binding part and
acts as the sole alpha chain for DRB1, DRB3, DRB4 and DRB5. [provided by RefSeq, Jul 2008]

Role in inflammation

Multiple studies have reported associations between HLA-DR or -DQ phenotypes and either
ulcerative colitis or Crohn's disease,
Furthermore, decreased monocyte surface protein expression of human leucocyte antigen DR (HLA-
DR) is a marker for changes of the innate immune response during sepsis. The contribution of HLA-
DR molecules to the pathogenesis of ulcerative colitis may be threefold larger when compared with
Crohn’s disease. Multiple studies have reported associations between HLA-DR or -DQ phenotypes
and either ulcerative colitis or Crohn’s disease

IL6 Gene

This gene encodes a cytokine that functions in inflammation and the maturation of B cells. In addition,
the encoded protein has been shown to be an endogenous pyrogen capable of inducing fever in
people with autoimmune diseases or infections. The protein is primarily produced at sites of acute and
chronic inflammation, where it is secreted into the serum and induces a transcriptional inflammatory
response through interleukin 6 receptor, alpha. The functioning of this gene is implicated in a wide
variety of inflammation-associated disease states, including suspectibility to diabetes mellitus and
systemic juvenile rheumatoid arthritis. Alternative splicing results in multiple transcript variants.
[provided by RefSeq, Dec 2015]

Role in inflammation

IL-6 has a dual effect; at some levels it acts as a defence mechanism but in chronic inflammation it is
rather proinflammatory. Interleukin-6 (IL-6) is a cytokine with redundant and pleiotropic activities, and
its synthesis is tightly regulated by transcriptional and posttranscriptional mechanisms. When
infections and tissue injuries occur, IL-6 synthesis is promptly induced and provides an emergent
signal that contributes to host defense through the stimulation of acute-phase responses, immune
reactions, and hematopoiesis. After the environmental stress is removed from the host, the production
of IL-6 is terminated. However, dysregulated continual synthesis of IL-6 is involved in the
development of chronic inflammatory autoimmune diseases. . There is growing evidence that the pro-
inflammatory cytokine interleukin (IL)-6 plays a crucial part in the uncontrolled intestinal inflammatory
process, which is a main characteristic of IBD.

An inactive form due to mutations or a constitutive high expression of NOD2 is associated with
several inflammatory diseases, suggesting that balanced NOD2 signaling is critical for the
maintenance of immune homeostasis

NOD2 Gene

 This gene is a member of the Nod1/Apaf-1 family and encodes a protein with two caspase
recruitment (CARD) domains and six leucine-rich repeats (LRRs). The protein is primarily
expressed in the peripheral blood leukocytes. It plays a role in the immune response to
intracellular bacterial lipopolysaccharides (LPS) by recognizing the muramyl dipeptide
(MDP) derived from them and activating the NFKB protein. Mutations in this gene have
been associated with Crohn disease and Blau syndrome. Alternatively spliced transcript
variants encoding distinct isoforms have been found for this gene. [provided by RefSeq,
Jun 2014]

Role in inflammation

NOD2 is able to detect intracellular muramyl dipeptide (MDP), a component of the bacterial wall
that is ubiquitously present in bacterial peptidoglycan.3 Upon activation by ligand, NOD2 mediates
innate immune response triggering proinflammatory responses. NOD2 mutation or altered
expression has been found in patients with chronic inflammatory disorders such as Crohn’s disease
(CD), Nod2 is an intracellular bacterial sensor and its mutations are associated with the development
of CD.
TLR2 Gene

 The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which
plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs
are highly conserved from Drosophila to humans and share structural and functional
similarities. This protein is a cell-surface protein that can form heterodimers with other TLR
family members to recognize conserved molecules derived from microorganisms known as
pathogen-associated molecular patterns (PAMPs). Activation of TLRs by PAMPs leads to
 an up-regulation of signaling pathways to modulate the host's inflammatory response. This
gene is also thought to promote apoptosis in response to bacterial lipoproteins. This gene
has been implicated in the pathogenesis of several autoimmune diseases. Alternative
splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

Role in inflammation

TLR2 forms heterodimers with TLR1 and TLR6, which is the initial step in a cascade of events leading
to significant innate immune responses, development of adaptive immunity to pathogens and
protection from immune sequelae related to infection with these pathogens. The inhibition of
TLR2/6 signaling has played a beneficial role by slowing down IBD progression

CASP1 Gene

 This gene encodes a protein which is a member of the cysteine-aspartic acid protease
(caspase) family. Sequential activation of caspases plays a central role in the execution-
phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic
processing at conserved aspartic residues to produce 2 subunits, large and small, that
dimerize to form the active enzyme. This gene was identified by its ability to proteolytically
cleave and activate the inactive precursor of interleukin-1, a cytokine involved in the
processes such as inflammation, septic shock, and wound healing. This gene has been
shown to induce cell apoptosis and may function in various developmental stages. Studies
of a similar gene in mouse suggest a role in the pathogenesis of Huntington disease.
Alternative splicing results in transcript variants encoding distinct isoforms. [provided by
RefSeq, Mar 2012]

 Role in inflammation

caspase-1 levels are elevated in both physiological and pathological conditions. Despite the
observation that merely raising caspase-1 levels is sufficient to induce inflammation,. inflammasome
induces the cleavage and activation of procaspase-1 which can then process interleukin-1 (IL-1)
family members such as IL-1α (Keller et al., 2008), IL-1β and IL-18 into their mature forms (Yu and
Finlay, 2008). In the context of wounding (Lee et al., 2009) as well as diseases with chronic
inflammation such as psoriasis (Johansen et al., 2007) heart disease (Merkle et al., 2007), gout and
arthritis (Church et al., 2008), there is an upregulation of procaspase-1 expression. Caspase-1
plays a fundamental role in innate immunity and in several important inflammatory diseases
as the protease activates the pro-inflammatory cytokines proIL-1β and proIL-18

HOXA4 Gene

 In vertebrates, the genes encoding the class of transcription factors called homeobox genes
are found in clusters named A, B, C, and D on four separate chromosomes. Expression of
these proteins is spatially and temporally regulated during embryonic development. This
gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription
factor which may regulate gene expression, morphogenesis, and differentiation. [provided
by RefSeq, Jul 2008]

Role in inflammation
HOXa4 gene expression was downregulated in UC mucosa compared to normal mucosa whether
colonic inflammation exists or not and this gene expression in colon cancer tissue was also
significantly lower than normal mucosa with additional RT-PCR. The HOXA4 transcript levels were
significantly decreased in human abdominal aortic aneurysms (AAAs) compared to age-matched
non-aneurysmal controls (P < 0.00004)
IL8 Gene:

The protein encoded by this gene is a member of the CXC chemokine family. This chemokine
is one of the major mediators of the inflammatory response. This chemokine is secreted by
several cell types. It functions as a chemoattractant, and is also a potent angiogenic factor.
This gene is believed to play a role in the pathogenesis

of bronchiolitis, a common respiratory tract disease caused by viral infection. This gene and
other ten members

of the CXC chemokine gene family form a chemokine gene cluster in a region mapped to
chromosome 4q. (provided by

RefSeq, Jul 2008)

Role in inflammation

Interleukin-8 (IL-8) is a chemoattractant cytokine produced by a variety of tissue and blood cells. IL-8
plays an important but nonspecific role in the pathogenesis of inflammatory bowel disease and that
the production ofIL-8 messenger RNA is restricted to areas with histological signs of inflammatory
activity and mucosal destruction. IL-8 protein concentrations are increased in inflamed intestinal IBD
mucosa, whereas intestinal IL-8 nlRNA transcript levels, which were not detectable in IBS, were
increased in active colonic CD but not in UC

PYCARD Gene

 This gene encodes an adaptor protein that is composed of two protein-protein interaction
domains: a N-terminal PYRIN-PAAD-DAPIN domain (PYD) and a C-terminal caspase-
recruitment domain (CARD). The PYD and CARD domains are members of the six-helix
bundle death domain-fold superfamily that mediates assembly of large signaling complexes
in the inflammatory and apoptotic signaling pathways via the activation of caspase. In
normal cells, this protein is localized to the cytoplasm; however, in cells undergoing
apoptosis, it forms ball-like aggregates near the nuclear periphery. Two transcript variants
encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Role in inflammation

The expression of PYCARD and NF-kappaB (p105/p50) protein was significantly higher in the PG
(Primary gout)group . upregulation of pro-inflammatory genes already begins at
the induction and execution phases of RD. These genes include NLRP3 inflammasome components
(NLRP3, PYCARD and CASP1), as well as the caspase-1-dependent pro-inflammatory cytokines
(IL1B and IL18) and their receptors. The top 20 predicted novel IBD genes (not reported in
any of the four sources of Fig. 4) based on p-values are IKBKG, BIRC3, BCL10,
RNF31, RBCK1, CCRL1, LAMC3, CARD11, KISS1, THBS2, TRAF2, TRAF1,
PYCARD, MIS12, ALB, AR, RIPK1, SHARPIN, SNAPIN and ITGA2B. To form the
basic Inflammasome subunit, the adaptor protein ASC (encoded by the PYCARD
gene) links the NLR sensor to caspase-1 [54]
TLR4 Gene

 The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which
plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs
are highly conserved from Drosophila to humans and share structural and functional
similarities. They recognize pathogen-associated molecular patterns that are expressed on
infectious agents, and mediate the production of cytokines necessary for the development
of effective immunity. The various TLRs exhibit different patterns of expression. This
receptor has been implicated in signal transduction events induced by lipopolysaccharide
(LPS) found in most gram-negative bacteria. Mutations in this gene have been associated
with differences in LPS responsiveness. Multiple transcript variants encoding different
isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

Role in inflammation

Toll-like receptor 4 (TLR4), in combination with CD14, LBP, and MD-2, acts as
the PRR for the lipid A moiety of lipopolysaccharide, a major component of
gram negative bacteria. TLR4 SNPs, rs4986790A>G and rs4986791C>T, are intimately
associated with increased risk of IBD. TLR4 Asp299Gly is associated with CD and UC susceptibility in
Caucasians, but not Asians. TLR4 Thr399Ile may be associated with IBD susceptibility in Caucasians
only.

CCL3 Gene

 This locus represents a small inducible cytokine. The encoded protein, also known as
macrophage inflammatory protein 1 alpha, plays a role in inflammatory responses through
binding to the receptors CCR1, CCR4 and CCR5. Polymorphisms at this locus may be
associated with both resistance and susceptibility to infection by human immunodeficiency
virus type 1.[provided by RefSeq, Sep 2010]

Role in inflammation

onocytes, which differentiate into macrophages, migrate to inflammatory sites in response to an

array of pro-inflammatory CC chemokines including MCP-1 (CCL2), MIP1α (CCL3), MIP-1β (CCL4),
RANTES (CCL5), MCP-4 (CCL13), HCC1 (CCL14), HCC2 (CCL15), HCC4 (CCL16). In addition, these
chemokines also attract NK cells, T cells, and immature dendritic cells (DC). Although CCL3,
CCL4, CCL5, CCL7, and CCL22 attract many different cell types such as eosinophils,
neutrophils, macrophages, Treg, Th1, and/or Th2 cells [16, 18, 19], decreased
numbers of CD4+ T cells detected by us in MC patients Microscopic colitis (MC)
Furthermore, the evidence that CCR5-deficient mice are resistant to DSS-induced colitis supports the
notion that CCR5 ligands, CCL3, CCL4, and CCL5, are involved in the progression of IBD

HSPA1A Gene

 This intronless gene encodes a 70kDa heat shock protein which is a member of the heat
shock protein 70 family. In conjuction with other heat shock proteins, this protein stabilizes
existing proteins against aggregation and mediates the folding of newly translated proteins
in the cytosol and in organelles. It is also involved in the ubiquitin-proteasome pathway
through interaction with the AU-rich element RNA-binding protein 1. The gene is located in
the major histocompatibility complex class III region, in a cluster with two closely related
genes which encode similar proteins. [provided by RefSeq, Jul 2008]

Role in inflammation

data suggest that HSPA1L might play a common pathogenic role in IBD. HSPA1L is constitutively
expressed, but its expression is at a lower level compared to other members of the HSP70 family,
such as HSPA1A and HSPA1B. Hspa1a, which encodes HSP70, is a STAT3 target gene and does not
contain NF-B binding sites in its promoter region and is not known to be induced by IKK activators.
IRAK1 Gene

 This gene encodes the interleukin-1 receptor-associated kinase 1, one of two putative
serine/threonine kinases that become associated with the interleukin-1 receptor (IL1R)
upon stimulation. This gene is partially responsible for IL1-induced upregulation of the
transcription factor NF-kappa B. Alternatively spliced transcript variants encoding different
isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Role in inflammation

IRAK1 signaling in T cells for Th cell differentiation and effector function in the intestine during
development of colitis. We show that IL-1β promotes Th17 cell development by inducing IL-23R
expression in an IRAK1-dependent manner. Furthermore, our results indicate that IRAK1 signaling in T
cells promotes the generation of proinflammatory IFN-γ– and IL-17–producing Th cells in vivo and is
required for their accumulation in the colon during colitis development induced by T cell transfer. Irak1-
deficient T cells showed a lower expression of genes involved in T cell activation, differentiation, and gut
homing, which correlated with a reduced capacity to induce experimental colitis in mice. Thus, IRAK1-
mediated signaling in CD4+ T cells drives their differentiation into proinflammatory effector cells and is
critical for their accumulation in the inflamed intestine.
RELA Gene

 NF-kappa-B is a ubiquitous transcription factor involved in several biological processes. It is

held in the cytoplasm in an inactive state by specific inhibitors. Upon degradation of the
inhibitor, NF-kappa-B moves to the nucleus and activates transcription of specific genes.
NF-kappa-B is composed of NFKB1 or NFKB2 bound to either REL, RELA, or RELB. The
most abundant form of NF-kappa-B is NFKB1 complexed with the product of this gene,
RELA. Four transcript variants encoding different isoforms have been found for this gene.
[provided by RefSeq, Sep 2011]

Role in inflammation

loss of RelA/p65 in the myeloid lineage leads to decreased DSS-induced CCL11 secretion, eosinophil
recruitment, IL-6 secretion and histopathology. RelA/p65 activation in the expression of
monocyte/MΦ-derived CCL11 in human IBD. RELA knockout mice is embryonic lethal due to liver
apoptosis.[8] Lymphocyte activation failure is also observed, suggesting that RELA is
indispensable in the proper development of the immune system. In comparison, deletion of other
REL-related genes will not cause embryonic development failure, though different levels of
defects are also noted.[8] The fact that cytokines such as TNFα and IL-1 can stimulate the
activation of RELA also supports its participation in immune response. In general, RELA
participates in adaptive immunity and responses to invading pathogens via NF-κB activation.
Mice without individual NF-κB proteins are deficient in B- and T-cell activation and proliferation,
cytoline production and isotype switching.[8] Mutations in RELA is found responsible for
inflammatory bowel disease as well.

TNF Gene

 This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor
necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can
bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and
TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of
biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism,
and coagulation. This cytokine has been implicated in a variety of diseases, including
autoimmune diseases, insulin resistance, and cancer. Knockout studies in mice also
suggested the neuroprotective function of this cytokine. [provided by RefSeq, Jul 2008]

Role in inflammation

TNF-β (+252A/G) polymorphisms showed a significant increase in the frequency of the GG genotype
in IBD patients, suggesting a positive association of GG genotype with IBD risk. High serum levels of
TNF-α together with the increased expression of TNF-α have been documented in intestinal tissues
and peripheral phagocytes of patients with IBD.13–15 It has also been shown that monoclonal
antibodies against TNF-α are effective for decreasing inflammation in IBD.16 Muro et al58 suggested
that TNF-α and -β play an important role in inflammatory response, and IBD is commonly treated
with TNF-α inhibitors. Additionally, as polymorphisms of TNF-α gene affect the gene expression
level, particular TNF-α genotypes may influence the response of IBD patients treated with TNF-α
inhibitors.