KEGG   PATHWAY: epz05323
Entry
epz05323                    Pathway                                
Name
Rheumatoid arthritis - Equus przewalskii (Przewalski's 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
epz05323  Rheumatoid arthritis
epz05323

Organism
Equus przewalskii (Przewalski's horse) [GN:epz]
Gene
103547416  CD80; CD80 molecule [KO:K05412]
103548423  CD86; CD86 molecule [KO:K05413]
103557389  CD28; CD28 molecule [KO:K06470]
103557388  CTLA4; cytotoxic T-lymphocyte associated protein 4 [KO:K06538]
103544254  boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
103544529  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
103544628  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
103540140  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
103540141  HLA class II histocompatibility antigen, DM alpha chain [KO:K06752]
103540143  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
103540328  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
103540329  boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
103541526  HLA class II histocompatibility antigen, DQ beta 2 chain-like [KO:K06752]
103544948  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
103542554  H-2 class II histocompatibility antigen, E-S beta chain-like [KO:K06752]
103543619  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
103545686  H-2 class II histocompatibility antigen, A-U alpha chain-like [KO:K06752]
103543091  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
103545626  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
103543208  mamu class II histocompatibility antigen, DR alpha chain [KO:K06752]
103545294  HLA class II histocompatibility antigen, DRB1-4 beta chain-like [KO:K06752]
103541108  uncharacterized LOC103541108 [KO:K10784]
103567401  uncharacterized LOC103567401 [KO:K10784]
103564100  uncharacterized LOC103564100 [KO:K10785]
103542083  uncharacterized LOC103542083 [KO:K10785]
103547219  ITGAL; integrin subunit alpha L [KO:K05718]
103543384  integrin beta-2-like [KO:K06464]
103558066  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
103549146  IL15; interleukin 15 [KO:K05433]
103557716  TNFSF13; tumor necrosis factor superfamily member 13 [KO:K05475]
103540324  TNFSF13B; tumor necrosis factor superfamily member 13b [KO:K05476]
103562625  uncharacterized LOC103562625 [KO:K06856]
103562621  putative V-set and immunoglobulin domain-containing protein 7 [KO:K06856]
103562494  LTB; lymphotoxin beta [KO:K03157]
103562469  TNF; tumor necrosis factor [KO:K03156]
103559673  IL1A; interleukin 1 alpha [KO:K04383]
103544835  IL1B; interleukin 1 beta [KO:K04519]
103561141  IL6; interleukin 6 [KO:K05405]
103565880  IL18; interleukin 18 [KO:K05482]
103553736  TLR2; toll like receptor 2 [KO:K10159]
103562040  TLR4; toll like receptor 4 [KO:K10160]
103548618  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
103562543  TGFB1; transforming growth factor beta 1 [KO:K13375]
103543045  TGFB2; transforming growth factor beta 2 [KO:K13376]
103555506  TGFB3; transforming growth factor beta 3 [KO:K13377]
103557547  IL23A; interleukin 23 subunit alpha [KO:K05426]
103550834  IL17A; interleukin 17A [KO:K05489]
103552001  PTH; parathyroid hormone [KO:K05261]
103557529  CSF1; colony stimulating factor 1 [KO:K05453]
103560371  TNFSF11; tumor necrosis factor superfamily member 11 [KO:K05473]
103562575  TNFRSF11A; TNF receptor superfamily member 11a [KO:K05147]
103552845  ATP6V1A; ATPase H+ transporting V1 subunit A [KO:K02145] [EC:7.1.2.2]
103564546  ATP6V1B1; ATPase H+ transporting V1 subunit B1 [KO:K02147]
103561145  ATP6V1B2; ATPase H+ transporting V1 subunit B2 [KO:K02147]
103565093  ATP6V1C1; ATPase H+ transporting V1 subunit C1 [KO:K02148]
103557399  ATP6V1C2; ATPase H+ transporting V1 subunit C2 [KO:K02148]
103562306  ATP6V1D; ATPase H+ transporting V1 subunit D [KO:K02149]
103559200  ATP6V1E1; ATPase H+ transporting V1 subunit E1 [KO:K02150]
103565438  ATP6V1E2; ATPase H+ transporting V1 subunit E2 [KO:K02150]
103544817  ATP6V1F; ATPase H+ transporting V1 subunit F [KO:K02151]
103561344  ATP6V1G1; ATPase H+ transporting V1 subunit G1 [KO:K02152]
103548365  V-type proton ATPase subunit G 3-like [KO:K02152]
103562465  ATP6V1G2; ATPase H+ transporting V1 subunit G2 [KO:K02152]
103556374  ATP6V1G3; ATPase H+ transporting V1 subunit G3 [KO:K02152]
103542955  ATP6V0E1; ATPase H+ transporting V0 subunit e1 [KO:K02153]
103549891  ATP6V0A2; ATPase H+ transporting V0 subunit a2 [KO:K02154]
103550363  ATP6V0A1; ATPase H+ transporting V0 subunit a1 [KO:K02154]
103559330  ATP6V0A4; ATPase H+ transporting V0 subunit a4 [KO:K02154]
103542463  ATP6V0D1; ATPase H+ transporting V0 subunit d1 [KO:K02146]
103567953  ATP6V0D2; ATPase H+ transporting V0 subunit d2 [KO:K02146]
103567788  ATP6V1H; ATPase H+ transporting V1 subunit H [KO:K02144]
103544129  ATP6AP1; ATPase H+ transporting accessory protein 1 [KO:K03662]
103551640  ATP6V0C; ATPase H+ transporting V0 subunit c [KO:K02155]
103561720  V-type proton ATPase 16 kDa proteolipid subunit [KO:K02155]
103548279  ATP6V0B; ATPase H+ transporting V0 subunit b [KO:K03661]
103547638  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
103562319  ACP5; acid phosphatase 5, tartrate resistant [KO:K14379] [EC:3.1.3.2]
103552636  MMP1; matrix metallopeptidase 1 [KO:K01388] [EC:3.4.24.7]
103552637  MMP3; matrix metallopeptidase 3 [KO:K01394] [EC:3.4.24.17]
103563220  cathepsin L1 [KO:K01365] [EC:3.4.22.15]
103550840  CTSL; cathepsin L [KO:K01365] [EC:3.4.22.15]
103556575  CSF2; colony stimulating factor 2 [KO:K05427]
103554508  CCL5; C-C motif chemokine ligand 5 [KO:K12499]
103543272  C-C motif chemokine 2 [KO:K14624]
103554513  C-C motif chemokine 3-like [KO:K05408]
103554512  C-C motif chemokine 3-like 1 [KO:K05408]
103546383  CCL20; C-C motif chemokine ligand 20 [KO:K14625]
103565789  growth-regulated alpha protein-like [KO:K05505]
103565792  uncharacterized LOC103565792 [KO:K05505]
103566767  C-X-C motif chemokine 6 [KO:K05506]
103566768  CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
103561655  CXCL12; C-X-C motif chemokine ligand 12 [KO:K10031]
103548136  VEGFA; vascular endothelial growth factor A [KO:K05448]
103561902  FLT1; fms related tyrosine kinase 1 [KO:K05096] [EC:2.7.10.1]
103553227  ANGPT1; angiopoietin 1 [KO:K05465]
103550275  TEK; TEK receptor tyrosine kinase [KO:K05121] [EC:2.7.10.1]
103559339  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
epz04370  VEGF signaling pathway
epz04380  Osteoclast differentiation
epz04620  Toll-like receptor signaling pathway
epz04659  Th17 cell differentiation
epz04660  T cell receptor signaling pathway
epz04670  Leukocyte transendothelial migration
KO pathway
ko05323   
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