KEGG   PATHWAY: ecb05323
Entry
ecb05323                    Pathway                                
Name
Rheumatoid arthritis - Equus caballus (horse)
Description
Rheumatoid arthritis (RA) is a chronic autoimmune joint disease where persistent inflammation affects bone remodeling leading to progressive bone destruction. In RA, abnormal activation of the immune system elevates pro-inflammatory cytokines and chemokines levels, which can promote synovial angiogenesis and leukocyte infiltration. The synovium forms a hyperplastic pannus with infiltrated macrophage-like and fibroblast-like synoviocytes and invades joints by secreting proteinases and inducing osteoclast differentiation.
Class
Human Diseases; Immune disease
Pathway map
ecb05323  Rheumatoid arthritis
ecb05323

Organism
Equus caballus (horse) [GN:ecb]
Gene
100071012  CD80; T-lymphocyte activation antigen CD80 [KO:K05412]
100060767  CD86; T-lymphocyte activation antigen CD86 isoform X5 [KO:K05413]
100067829  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
100067931  CTLA4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
100061035  HLA class II histocompatibility antigen, DM alpha chain-like precursor [KO:K06752]
100060770  HLA class II histocompatibility antigen, DO beta chain isoform X1 [KO:K06752]
100052249  DQA; MHC class II DQ-alpha precursor [KO:K06752]
100052310  DRB; MHC class II DR-beta chain precursor [KO:K06752]
100052364  DRB; MHC class II DR-beta chain precursor [KO:K06752]
100051944  DRA; MHC class II DR alpha chain precursor [KO:K06752]
100052184  DQB; MHC class II DQ-beta chain precursor [KO:K06752]
100061127  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
100060996  HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752]
100052006  DRB; MHC class II DR-beta chain precursor [KO:K06752]
100052125  DQA; MHC class II DQ-alpha chain precursor [KO:K06752]
100060531  HLA class II histocompatibility antigen, DQ beta 2 chain isoform X1 [KO:K06752]
100052063  DQA; MHC class II DQ-alpha chain [KO:K06752]
100060320  DQB; MHC class II DQ-beta chain precursor [KO:K06752]
111767457  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
100060697  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
111772100  uncharacterized protein LOC111772100 [KO:K10784]
106783094  uncharacterized protein LOC106783094 [KO:K10785]
100065508  ITGAL; integrin alpha-L isoform X2 [KO:K05718]
100056128  ITGB2; integrin beta-2 [KO:K06464]
100056049  integrin beta-2 [KO:K06464]
100058207  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
100034058  IL15; interleukin-15 [KO:K05433]
100147233  TNFSF13; tumor necrosis factor ligand superfamily member 13 [KO:K05475]
100051550  TNFSF13B; tumor necrosis factor ligand superfamily member 13B [KO:K05476]
100146643  immunoglobulin epsilon heavy chain [KO:K06856]
100058364  LTB; lymphotoxin-beta isoform X1 [KO:K03157]
100033834  TNF; tumor necrosis factor [KO:K03156]
100064969  IL1A; interleukin-1 alpha precursor [KO:K04383]
100034237  IL1B; interleukin-1 beta [KO:K04519]
100052414  IL1B; interleukin-1 beta [KO:K04519]
111768185  interleukin-1 beta-like [KO:K04519]
100034196  IL6; interleukin-6 precursor [KO:K05405]
100056037  IL11; interleukin-11 isoform X1 [KO:K05417]
100034216  IL18; interleukin-18 precursor [KO:K05482]
100009701  TLR2; toll-like receptor 2 precursor [KO:K10159]
100066890  TLR4; toll-like receptor 4 precursor [KO:K10160]
111771935  toll-like receptor 4 [KO:K10160]
100067469  JUN; transcription factor AP-1 [KO:K04448]
100051632  FOS; proto-oncogene c-Fos [KO:K04379]
100033900  TGFB1; transforming growth factor beta-1 precursor [KO:K13375]
100050377  TGFB2; transforming growth factor beta-2 isoform X2 [KO:K13376]
111771316  transforming growth factor beta-2-like isoform X1 [KO:K13376]
100051765  TGFB3; transforming growth factor beta-3 [KO:K13377]
100034230  IL23A; interleukin-23 subunit alpha precursor [KO:K05426]
100034142  IL17A; interleukin-17A precursor [KO:K05489]
100034104  PTH; parathyroid hormone precursor [KO:K05261]
100146493  CSF1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453]
100060254  TNFSF11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
100056617  TNFRSF11A; tumor necrosis factor receptor superfamily member 11A isoform X1 [KO:K05147]
100061223  ATP6V1A; V-type proton ATPase catalytic subunit A [KO:K02145] [EC:7.1.2.2]
100055525  ATP6V1B2; V-type proton ATPase subunit B, brain isoform [KO:K02147]
100050282  ATP6V1B1; V-type proton ATPase subunit B, kidney isoform [KO:K02147]
100057005  ATP6V1C2; V-type proton ATPase subunit C 2 isoform X5 [KO:K02148]
100056307  ATP6V1C1; V-type proton ATPase subunit C 1 [KO:K02148]
111767396  ATP6V1C1; V-type proton ATPase subunit C 1 isoform X1 [KO:K02148]
100052659  ATP6V1D; V-type proton ATPase subunit D [KO:K02149]
100053341  ATP6V1E2; V-type proton ATPase subunit E 2 [KO:K02150]
100049854  ATP6V1E1; V-type proton ATPase subunit E 1 [KO:K02150]
102148469  ATP6V1F; V-type proton ATPase subunit F [KO:K02151]
100051640  ATP6V1G3; V-type proton ATPase subunit G 3 [KO:K02152]
100064677  V-type proton ATPase subunit G 3-like [KO:K02152]
100051132  ATP6V1G1; V-type proton ATPase subunit G 1 [KO:K02152]
102150189  ATP6V1G2; V-type proton ATPase subunit G 2 [KO:K02152]
100069785  ATP6V0E1; V-type proton ATPase subunit e 1 [KO:K02153]
100629184  ATP6V0E2; V-type proton ATPase subunit e 2 [KO:K02153]
100052802  ATP6V0A1; V-type proton ATPase 116 kDa subunit a isoform X4 [KO:K02154]
100146660  TCIRG1; V-type proton ATPase 116 kDa subunit a isoform X1 [KO:K02154]
100064797  ATP6V0A4; V-type proton ATPase 116 kDa subunit a isoform X1 [KO:K02154]
100061140  ATP6V0A2; V-type proton ATPase 116 kDa subunit a [KO:K02154]
100049996  ATP6V0D2; V-type proton ATPase subunit d 2 isoform X1 [KO:K02146]
100053316  ATP6V0D1; V-type proton ATPase subunit d 1 [KO:K02146]
100054947  ATP6V1H; V-type proton ATPase subunit H isoform X1 [KO:K02144]
100630677  ATP6AP1; V-type proton ATPase subunit S1 [KO:K03662]
100065783  ATP6V0C; V-type proton ATPase 16 kDa proteolipid subunit [KO:K02155]
100146553  ATP6V0B; V-type proton ATPase 21 kDa proteolipid subunit [KO:K03661]
100054991  CTSK; cathepsin K isoform X2 [KO:K01371] [EC:3.4.22.38]
100056621  ACP5; tartrate-resistant acid phosphatase type 5 precursor [KO:K14379] [EC:3.1.3.2]
100033896  MMP1; interstitial collagenase precursor [KO:K01388] [EC:3.4.24.7]
100034195  MMP3; stromelysin-1 precursor [KO:K01394] [EC:3.4.24.17]
100061234  cathepsin L1 isoform X1 [KO:K01365] [EC:3.4.22.15]
100061532  CTSL; cathepsin L1 [KO:K01365] [EC:3.4.22.15]
100033981  CSF2; granulocyte-macrophage colony-stimulating factor precursor [KO:K05427]
100033925  CCL5; C-C motif chemokine 5 precursor [KO:K12499]
100034136  CCL2; C-C motif chemokine 2 precursor [KO:K14624]
100057909  CCL3; C-C motif chemokine 3 precursor [KO:K05408]
100629808  CCL20; C-C motif chemokine 20 isoform X1 [KO:K14625]
100034121  CXCL1; chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha) precursor [KO:K05505]
100233237  CXCL2; C-X-C motif chemokine 2 precursor [KO:K05505]
100056258  MIP-2BETA; uncharacterized protein LOC100056258 precursor [KO:K05505]
100033988  CXCL6; C-X-C motif chemokine 6 precursor [KO:K05506]
100037400  CXCL8; interleukin-8 precursor [KO:K10030]
100049872  CXCL12; stromal cell-derived factor 1 isoform X1 [KO:K10031]
100033839  VEGFA; vascular endothelial growth factor A precursor [KO:K05448]
100033957  FLT1; vascular endothelial growth factor receptor 1 precursor [KO:K05096] [EC:2.7.10.1]
100056482  ANGPT1; angiopoietin-1 isoform X1 [KO:K05465]
100066963  TEK; angiopoietin-1 receptor [KO:K05121] [EC:2.7.10.1]
100034181  IFNG; interferon gamma precursor [KO:K04687]
Compound
C00080  H+
C00584  Prostaglandin E2
C05443  Vitamin D3
Reference
PMID:16127012
  Authors
Zwerina J, Redlich K, Schett G, Smolen JS
  Title
Pathogenesis of rheumatoid arthritis: targeting cytokines.
  Journal
Ann N Y Acad Sci 1051:716-29 (2005)
DOI:10.1196/annals.1361.116
Reference
PMID:20036936
  Authors
Szekanecz Z, Vegvari A, Szabo Z, Koch AE
  Title
Chemokines and chemokine receptors in arthritis.
  Journal
Front Biosci (Schol Ed) 2:153-67 (2010)
DOI:10.2741/53
Reference
PMID:20651747
  Authors
Isaacs JD
  Title
The changing face of rheumatoid arthritis: sustained remission for all?
  Journal
Nat Rev Immunol 10:605-11 (2010)
DOI:10.1038/nri2804
Reference
PMID:17195034
  Authors
Strand V, Kimberly R, Isaacs JD
  Title
Biologic therapies in rheumatology: lessons learned, future directions.
  Journal
Nat Rev Drug Discov 6:75-92 (2007)
DOI:10.1038/nrd2196
Reference
PMID:20193003
  Authors
Bartok B, Firestein GS
  Title
Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis.
  Journal
Immunol Rev 233:233-55 (2010)
DOI:10.1111/j.0105-2896.2009.00859.x
Reference
PMID:17502360
  Authors
Dai SM, Shan ZZ, Xu H, Nishioka K
  Title
Cellular targets of interleukin-18 in rheumatoid arthritis.
  Journal
Ann Rheum Dis 66:1411-8 (2007)
DOI:10.1136/ard.2006.067793
Reference
PMID:9627005
  Authors
Koch AE
  Title
Review: angiogenesis: implications for rheumatoid arthritis.
  Journal
Arthritis Rheum 41:951-62 (1998)
DOI:10.1002/1529-0131(199806)41:6<951::AID-ART2>3.0.CO;2-D
Reference
PMID:20305562
  Authors
Szekanecz Z, Besenyei T, Szentpetery A, Koch AE
  Title
Angiogenesis and vasculogenesis in rheumatoid arthritis.
  Journal
Curr Opin Rheumatol 22:299-306 (2010)
DOI:10.1097/BOR.0b013e328337c95a
Reference
PMID:15059264
  Authors
Brunner-Weinzierl MC, Hoff H, Burmester GR
  Title
Multiple functions for CD28 and cytotoxic T lymphocyte antigen-4 during different phases of T cell responses: implications for arthritis and autoimmune diseases.
  Journal
Arthritis Res Ther 6:45-54 (2004)
DOI:10.1186/ar1158
Reference
PMID:11861618
  Authors
Theill LE, Boyle WJ, Penninger JM
  Title
RANK-L and RANK: T cells, bone loss, and mammalian evolution.
  Journal
Annu Rev Immunol 20:795-823 (2002)
DOI:10.1146/annurev.immunol.20.100301.064753
Reference
PMID:19184540
  Authors
Mensah KA, Li J, Schwarz EM
  Title
The emerging field of osteoimmunology.
  Journal
Immunol Res 45:100-13 (2009)
DOI:10.1007/s12026-009-8093-x
Reference
PMID:16313349
  Authors
Takayanagi H, Sato K, Takaoka A, Taniguchi T
  Title
Interplay between interferon and other cytokine systems in bone metabolism.
  Journal
Immunol Rev 208:181-93 (2005)
DOI:10.1111/j.0105-2896.2005.00337.x
Reference
PMID:20392226
  Authors
Takayanagi H
  Title
New immune connections in osteoclast formation.
  Journal
Ann N Y Acad Sci 1192:117-23 (2010)
DOI:10.1111/j.1749-6632.2009.05303.x
Reference
PMID:19585227
  Authors
Nakashima T, Takayanagi H
  Title
Osteoimmunology: crosstalk between the immune and bone systems.
  Journal
J Clin Immunol 29:555-67 (2009)
DOI:10.1007/s10875-009-9316-6
Reference
PMID:19455385
  Authors
Nakashima T, Takayanagi H
  Title
Osteoclasts and the immune system.
  Journal
J Bone Miner Metab 27:519-29 (2009)
DOI:10.1007/s00774-009-0089-z
Reference
PMID:17380158
  Authors
Takayanagi H
  Title
Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems.
  Journal
Nat Rev Immunol 7:292-304 (2007)
DOI:10.1038/nri2062
Reference
PMID:20510236
  Authors
Fox DA, Gizinski A, Morgan R, Lundy SK
  Title
Cell-cell interactions in rheumatoid arthritis synovium.
  Journal
Rheum Dis Clin North Am 36:311-23 (2010)
DOI:10.1016/j.rdc.2010.02.004
Reference
PMID:15055519
  Authors
Rho J, Takami M, Choi Y
  Title
Osteoimmunology: interactions of the immune and skeletal systems.
  Journal
Mol Cells 17:1-9 (2004)
Related
pathway
ecb04370  VEGF signaling pathway
ecb04380  Osteoclast differentiation
ecb04620  Toll-like receptor signaling pathway
ecb04659  Th17 cell differentiation
ecb04660  T cell receptor signaling pathway
ecb04670  Leukocyte transendothelial migration
KO pathway
ko05323   
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