KEGG   PATHWAY: cge05321
Entry
cge05321                    Pathway                                
Name
Inflammatory bowel disease - Cricetulus griseus (Chinese hamster)
Description
Inflammatory bowel disease (IBD), which includes Crohn disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation of the gastrointestinal tract due to environmental and genetic factors, infectious microbes, and the dysregulated immune system. Although many environmental factors (for example, geographic locations, smoking, etc.) affect the development of IBD, the most crucial might be the luminal (external) environment of the epithelial cells. There are pathogens that are found in increasing frequency in IBD. The microbial components such as flagellin, peptidoglycan, and lipopolysaccharide are recognized by receptors such as toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD) proteins, and also by antigen-presenting cells (APCs) in genetically susceptible host. The TLR recognition triggers the activation of NF-kappaB, leading to an inflammatory response. APC-expressed gene NOD2 has been associated with Crohn disease. In case of mutations of NOD2, negative regulation of IL-12 production is reduced with the stimulation of muramyl dipeptide (MDP), leading to CD. In addition, the APC mediates the differentiation of naive T cells into effector T cells (Th1, Th17, Th2) and natural killer T (NKT) cells. Th1 and Th17 cells produce high levels of IFN-gamma and IL-17, -22, respectively, both of which promote CD. In contrast, Th2 cells produce IL-4, -5, -10, which together with IL-13 from NKT induce UC.
Class
Human Diseases; Immune disease
Pathway map
cge05321  Inflammatory bowel disease
cge05321

Organism
Cricetulus griseus (Chinese hamster) [GN:cge]
Gene
100771475  Tlr2; LOW QUALITY PROTEIN: toll-like receptor 2 [KO:K10159]
100689329  Tlr4; toll-like receptor 4 precursor [KO:K10160]
100772103  Tlr5; toll-like receptor 5 [KO:K10168]
100770607  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X3 [KO:K02580]
100763542  Rela; transcription factor p65 isoform X4 [KO:K04735]
100759694  Nod2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165]
100750512  H-2 class II histocompatibility antigen, E-S beta chain isoform X2 [KO:K06752]
100759913  RLA class II histocompatibility antigen, DP alpha-1 chain [KO:K06752]
100760208  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
100759342  HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752]
100760794  class II histocompatibility antigen, M alpha chain [KO:K06752]
103161518  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
100761373  rano class II histocompatibility antigen, A beta chain isoform X2 [KO:K06752]
100752328  H-2 class II histocompatibility antigen, I-E alpha chain [KO:K06752]
100761951  LOW QUALITY PROTEIN: H-2 class II histocompatibility antigen, I-E beta chain-like [KO:K06752]
100766775  LOW QUALITY PROTEIN: H-2 class II histocompatibility antigen, E-S beta chain-like isoform X2 [KO:K06752]
100767068  H-2 class II histocompatibility antigen, E-D beta chain [KO:K06752]
100762240  H-2 class II histocompatibility antigen, E-D beta chain-like isoform X2 [KO:K06752]
100767639  H-2 class II histocompatibility antigen, E-U alpha chain isoform X2 [KO:K06752]
100774703  LOW QUALITY PROTEIN: H-2 class II histocompatibility antigen, E-S beta chain [KO:K06752]
100761082  class II histocompatibility antigen, M beta 1 chain [KO:K06752]
100757609  T-cell receptor beta-2 chain C region [KO:K10785]
100768486  Ifng; interferon gamma isoform X2 [KO:K04687]
100772793  Ifngr1; interferon gamma receptor 1 [KO:K05132]
100768877  Ifngr2; interferon gamma receptor 2 isoform X3 [KO:K05133]
100755609  Stat1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
100762313  Tbx21; T-box transcription factor TBX21 isoform X2 [KO:K10166]
100755642  Il4; interleukin-4 [KO:K05430]
100755060  Il5; interleukin-5 [KO:K05428]
100760602  Il12a; interleukin-12 subunit alpha [KO:K05406]
100764758  Il12b; interleukin-12 subunit beta [KO:K05425]
100758602  Il12rb2; interleukin-12 receptor subunit beta-2 isoform X1 [KO:K05064]
100763378  Il12rb1; interleukin-12 receptor subunit beta-1 isoform X3 [KO:K05063]
100769249  signal transducer and activator of transcription 4 isoform X3 [KO:K11222]
100755773  Il2; interleukin-2 [KO:K05429]
100750469  Il18; interleukin-18 isoform X1 [KO:K05482]
100758160  Il18r1; interleukin-18 receptor 1 [KO:K05173]
100757868  Il18rap; interleukin-18 receptor accessory protein [KO:K05174]
113834001  transcription factor AP-1 [KO:K04448]
100764780  Tnf; tumor necrosis factor isoform X1 [KO:K03156]
100689186  Il6; interleukin-6 [KO:K05405]
100769260  Il1a; interleukin-1 alpha [KO:K04383]
100775079  Il1b; interleukin-1 beta [KO:K04519]
100773359  Tgfb1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375]
100774918  Tgfb2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
100756831  Tgfb3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
100771578  Smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
100759220  Smad3; mothers against decapentaplegic homolog 3 isoform X3 [KO:K23605]
100755865  Stat3; signal transducer and activator of transcription 3 isoform X9 [KO:K04692]
100755479  Il21; interleukin-21 [KO:K05434]
100763133  Il21r; LOW QUALITY PROTEIN: interleukin-21 receptor [KO:K05075]
100765061  Il23a; interleukin-23 subunit alpha [KO:K05426]
100758310  Il23r; interleukin-23 receptor [KO:K05065]
100769044  Rorc; nuclear receptor ROR-gamma isoform X2 [KO:K08534]
100759952  Rora; nuclear receptor ROR-alpha isoform X2 [KO:K08532]
100757421  Foxp3; forkhead box protein P3 [KO:K10163]
100750422  Il17a; interleukin-17A [KO:K05489]
100751004  Il17f; interleukin-17F isoform X2 [KO:K05494]
100768781  Il22; interleukin-22 [KO:K05445]
100762840  Il4r; interleukin-4 receptor subunit alpha isoform X1 [KO:K05071]
100756284  Il2rg; cytokine receptor common subunit gamma [KO:K05070]
100753838  Stat6; signal transducer and activator of transcription 6 isoform X1 [KO:K11225]
100760238  Gata3; trans-acting T-cell-specific transcription factor GATA-3 isoform X1 [KO:K17895]
100759320  Il10; interleukin-10 isoform X1 [KO:K05443]
100762597  Il13; interleukin-13 [KO:K05435]
113835141  transcription factor Maf [KO:K09035]
100764851  Nfatc1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X2 [KO:K04446]
Reference
  Authors
Melmed GY, Targan SR
  Title
Future biologic targets for IBD: potentials and pitfalls.
  Journal
Nat Rev Gastroenterol Hepatol 7:110-7 (2010)
DOI:10.1038/nrgastro.2009.218
Reference
  Authors
Shih DQ, Targan SR
  Title
Immunopathogenesis of inflammatory bowel disease.
  Journal
World J Gastroenterol 14:390-400 (2008)
DOI:10.3748/wjg.14.390
Reference
  Authors
Baumgart DC, Carding SR
  Title
Inflammatory bowel disease: cause and immunobiology.
  Journal
Lancet 369:1627-40 (2007)
DOI:10.1016/S0140-6736(07)60750-8
Reference
  Authors
Strober W, Murray PJ, Kitani A, Watanabe T
  Title
Signalling pathways and molecular interactions of NOD1 and NOD2.
  Journal
Nat Rev Immunol 6:9-20 (2006)
DOI:10.1038/nri1747
Reference
  Authors
Matricon J, Barnich N, Ardid D
  Title
Immunopathogenesis of inflammatory bowel disease.
  Journal
Self Nonself 1:299-309 (2010)
DOI:10.4161/self.1.4.13560
Reference
  Authors
Agnello D, Lankford CS, Bream J, Morinobu A, Gadina M, O'Shea JJ, Frucht DM
  Title
Cytokines and transcription factors that regulate T helper cell differentiation: new players and new insights.
  Journal
J Clin Immunol 23:147-61 (2003)
DOI:10.1023/A:1023381027062
Reference
  Authors
Glimcher LH, Murphy KM
  Title
Lineage commitment in the immune system: the T helper lymphocyte grows up.
  Journal
Genes Dev 14:1693-711 (2000)
DOI:10.1101/gad.14.14.1693
Reference
  Authors
Neurath MF, Finotto S, Glimcher LH
  Title
The role of Th1/Th2 polarization in mucosal immunity.
  Journal
Nat Med 8:567-73 (2002)
DOI:10.1038/nm0602-567
Reference
  Authors
Afkarian M, Sedy JR, Yang J, Jacobson NG, Cereb N, Yang SY, Murphy TL, Murphy KM
  Title
T-bet is a STAT1-induced regulator of IL-12R expression in naive CD4+ T cells.
  Journal
Nat Immunol 3:549-57 (2002)
DOI:10.1038/ni794
Reference
  Authors
Sartor RB
  Title
Microbial influences in inflammatory bowel diseases.
  Journal
Gastroenterology 134:577-94 (2008)
DOI:10.1053/j.gastro.2007.11.059
Reference
PMID:9759857
  Authors
Yoshimoto T, Takeda K, Tanaka T, Ohkusu K, Kashiwamura S, Okamura H, Akira S, Nakanishi K
  Title
IL-12 up-regulates IL-18 receptor expression on T cells, Th1 cells, and B cells: synergism with IL-18 for IFN-gamma production.
  Journal
J Immunol 161:3400-7 (1998)
Reference
  Authors
Hur SJ, Kang SH, Jung HS, Kim SC, Jeon HS, Kim IH, Lee JD
  Title
Review of natural products actions on cytokines in inflammatory bowel disease.
  Journal
Nutr Res 32:801-16 (2012)
DOI:10.1016/j.nutres.2012.09.013
Reference
  Authors
Bettelli E, Korn T, Oukka M, Kuchroo VK
  Title
Induction and effector functions of T(H)17 cells.
  Journal
Nature 453:1051-7 (2008)
DOI:10.1038/nature07036
Reference
  Authors
Ivanov II, Zhou L, Littman DR
  Title
Transcriptional regulation of Th17 cell differentiation.
  Journal
Semin Immunol 19:409-17 (2007)
DOI:10.1016/j.smim.2007.10.011
Reference
  Authors
Di Cesare A, Di Meglio P, Nestle FO
  Title
The IL-23/Th17 axis in the immunopathogenesis of psoriasis.
  Journal
J Invest Dermatol 129:1339-50 (2009)
DOI:10.1038/jid.2009.59
Reference
  Authors
Jetten AM
  Title
Retinoid-related orphan receptors (RORs): critical roles in development, immunity, circadian rhythm, and cellular metabolism.
  Journal
Nucl Recept Signal 7:e003 (2009)
DOI:10.1621/nrs.07003
Reference
  Authors
Bene L, Falus A, Baffy N, Fulop AK
  Title
Cellular and molecular mechanisms in the two major forms of inflammatory bowel disease.
  Journal
Pathol Oncol Res 17:463-72 (2011)
DOI:10.1007/s12253-011-9397-4
Related
pathway
cge04060  Cytokine-cytokine receptor interaction
cge04612  Antigen processing and presentation
cge04620  Toll-like receptor signaling pathway
cge04621  NOD-like receptor signaling pathway
cge04630  JAK-STAT signaling pathway
cge04659  Th17 cell differentiation
cge04660  T cell receptor signaling pathway
KO pathway
ko05321   
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