KEGG   PATHWAY: oro05323
Entry
oro05323                    Pathway                                
Name
Rheumatoid arthritis - Odobenus rosmarus divergens (Pacific walrus)
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
oro05323  Rheumatoid arthritis
oro05323

Organism
Odobenus rosmarus divergens (Pacific walrus) [GN:oro]
Gene
101363230  CD80; T-lymphocyte activation antigen CD80 [KO:K05412]
101386232  CD86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413]
101374233  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
101373461  CTLA4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
101372409  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP alpha 1 chain [KO:K06752]
101368848  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752]
101367969  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
101370206  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
101370503  HLA class II histocompatibility antigen, DQ beta 1 chain-like isoform X1 [KO:K06752]
101370728  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
101371503  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
101371809  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
101372107  HLA class II histocompatibility antigen, DM alpha chain [KO:K06752]
101379071  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
101379947  H-2 class II histocompatibility antigen, E-S beta chain-like [KO:K06752]
101380246  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
101380534  HLA class II histocompatibility antigen, DR alpha chain-like [KO:K06752]
101370679  ITGAL; integrin alpha-L [KO:K05718]
101383612  ITGB2; integrin beta-2 [KO:K06464]
101375646  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
101372500  IL15; interleukin-15 isoform X1 [KO:K05433]
101365786  tumor necrosis factor ligand superfamily member 13 isoform X1 [KO:K05475]
101377516  TNFSF13B; tumor necrosis factor ligand superfamily member 13B isoform X1 [KO:K05476]
101370467  uncharacterized protein LOC101370467 [KO:K06856]
101368500  LTB; lymphotoxin-beta isoform X1 [KO:K03157]
101368209  TNF; tumor necrosis factor [KO:K03156]
101382716  IL1A; interleukin-1 alpha isoform X1 [KO:K04383]
101383005  IL1B; interleukin-1 beta [KO:K04519]
101377851  IL6; interleukin-6 isoform X1 [KO:K05405]
101386986  IL11; interleukin-11 [KO:K05417]
101368106  IL18; interleukin-18 isoform X1 [KO:K05482]
101363280  TLR2; toll-like receptor 2 [KO:K10159]
101367407  uncharacterized protein LOC101367407 [KO:K10159]
101371071  TLR4; toll-like receptor 4 [KO:K10160]
101368207  JUN; transcription factor AP-1 isoform X1 [KO:K04448]
101366773  FOS; proto-oncogene c-Fos isoform X1 [KO:K04379]
101385166  TGFB1; transforming growth factor beta-1 [KO:K13375]
101380860  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
101364584  TGFB3; transforming growth factor beta-3 [KO:K13377]
101367844  IL23A; interleukin-23 subunit alpha [KO:K05426]
101368993  IL17A; interleukin-17A isoform X1 [KO:K05489]
101371642  PTH; parathyroid hormone [KO:K05261]
101365427  CSF1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453]
101376926  TNFSF11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
101379212  TNFRSF11A; tumor necrosis factor receptor superfamily member 11A [KO:K05147]
101365768  ATP6V1A; V-type proton ATPase catalytic subunit A [KO:K02145] [EC:7.1.2.2]
101379692  ATP6V1B2; V-type proton ATPase subunit B, brain isoform [KO:K02147]
101386479  ATP6V1B1; V-type proton ATPase subunit B, kidney isoform isoform X1 [KO:K02147]
101374595  ATP6V1C2; V-type proton ATPase subunit C 2 isoform X1 [KO:K02148]
101379625  ATP6V1C1; V-type proton ATPase subunit C 1 isoform X1 [KO:K02148]
101363014  ATP6V1D; V-type proton ATPase subunit D [KO:K02149]
101383455  V-type proton ATPase subunit E 1-like isoform X1 [KO:K02150]
101370142  ATP6V1E1; V-type proton ATPase subunit E 1 isoform X1 [KO:K02150]
101363332  ATP6V1E2; V-type proton ATPase subunit E 2 [KO:K02150]
101383372  ATP6V1F; V-type proton ATPase subunit F [KO:K02151]
101384010  V-type proton ATPase subunit G 1-like isoform X1 [KO:K02152]
101366940  ATP6V1G2; V-type proton ATPase subunit G 2 isoform X1 [KO:K02152]
101382997  ATP6V1G3; V-type proton ATPase subunit G 3 [KO:K02152]
101384685  ATP6V1G1; V-type proton ATPase subunit G 1 [KO:K02152]
101375691  ATP6V0E1; V-type proton ATPase subunit e 1 [KO:K02153]
101374243  ATP6V0E2; V-type proton ATPase subunit e 2 [KO:K02153]
101380850  V-type proton ATPase subunit e 1 [KO:K02153]
101382977  ATP6V0A2; V-type proton ATPase 116 kDa subunit a isoform 2 [KO:K02154]
101374534  ATP6V0A1; V-type proton ATPase 116 kDa subunit a isoform 1 isoform X2 [KO:K02154]
101381351  ATP6V0A4; V-type proton ATPase 116 kDa subunit a isoform 4 [KO:K02154]
101376099  TCIRG1; V-type proton ATPase 116 kDa subunit a isoform 3 [KO:K02154]
101363374  ATP6V0D1; V-type proton ATPase subunit d 1 [KO:K02146]
101374455  ATP6V0D2; V-type proton ATPase subunit d 2 [KO:K02146]
101375398  ATP6V1H; V-type proton ATPase subunit H isoform X1 [KO:K02144]
101382296  ATP6AP1; V-type proton ATPase subunit S1 [KO:K03662]
101382467  V-type proton ATPase 16 kDa proteolipid subunit-like [KO:K02155]
101377607  ATP6V0C; V-type proton ATPase 16 kDa proteolipid subunit [KO:K02155]
101365399  ATP6V0B; V-type proton ATPase 21 kDa proteolipid subunit isoform X1 [KO:K03661]
101371209  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
101365788  ACP5; tartrate-resistant acid phosphatase type 5 [KO:K14379] [EC:3.1.3.2]
101371070  LOW QUALITY PROTEIN: interstitial collagenase-like [KO:K01388] [EC:3.4.24.7]
101369292  interstitial collagenase-like [KO:K01388] [EC:3.4.24.7]
101368994  MMP3; stromelysin-1 [KO:K01394] [EC:3.4.24.17]
101362126  cathepsin L1 [KO:K01365] [EC:3.4.22.15]
101364724  cathepsin L1-like [KO:K01365] [EC:3.4.22.15]
101382346  cathepsin L1-like [KO:K01365] [EC:3.4.22.15]
101364428  cathepsin L1-like [KO:K01365] [EC:3.4.22.15]
101365120  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
101381338  CCL5; LOW QUALITY PROTEIN: C-C motif chemokine 5 [KO:K12499]
101377584  CCL2; C-C motif chemokine 2 [KO:K14624]
101370944  C-C motif chemokine 3 [KO:K05408]
101371244  C-C motif chemokine 3-like [KO:K05408]
101371529  regakine-1-like [KO:K05408]
105758121  C-C motif chemokine 3-like [KO:K05408]
101376905  CCL20; C-C motif chemokine 20 isoform X2 [KO:K14625]
101365347  growth-regulated protein homolog beta-like [KO:K05505]
101377249  growth-regulated protein homolog gamma-like [KO:K05505]
101376379  C-X-C motif chemokine 6 [KO:K05506]
101365039  CXCL8; interleukin-8 [KO:K10030]
101378047  CXCL12; stromal cell-derived factor 1 isoform X1 [KO:K10031]
101363442  VEGFA; vascular endothelial growth factor A [KO:K05448]
101383542  FLT1; vascular endothelial growth factor receptor 1 [KO:K05096] [EC:2.7.10.1]
101373650  ANGPT1; angiopoietin-1 isoform X1 [KO:K05465]
101367636  TEK; angiopoietin-1 receptor isoform X1 [KO:K05121] [EC:2.7.10.1]
101382125  IFNG; interferon gamma [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
oro04370  VEGF signaling pathway
oro04380  Osteoclast differentiation
oro04620  Toll-like receptor signaling pathway
oro04659  Th17 cell differentiation
oro04660  T cell receptor signaling pathway
oro04670  Leukocyte transendothelial migration
KO pathway
ko05323   
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