KEGG   PATHWAY: mlx05323
Entry
mlx05323                    Pathway                                
Name
Rheumatoid arthritis - Mirounga leonina (Southern elephant seal)
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
mlx05323  Rheumatoid arthritis
mlx05323

Organism
Mirounga leonina (Southern elephant seal) [GN:mlx]
Gene
118007066  CD80; T-lymphocyte activation antigen CD80 [KO:K05412]
118007039  CD86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413]
118012117  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
118011773  CTLA4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
118000598  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP alpha 1 chain [KO:K06752]
118000703  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
118000882  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP beta 1 chain-like [KO:K06752]
118001122  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
118001151  HLA class II histocompatibility antigen, DO alpha chain isoform X1 [KO:K06752]
118001168  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
118001169  DLA class II histocompatibility antigen, DR-1 beta chain isoform X1 [KO:K06752]
118001171  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
118001172  HLA class II histocompatibility antigen, DR alpha chain isoform X1 [KO:K06752]
117999594  ITGAL; integrin alpha-L isoform X1 [KO:K05718]
118026948  ITGB2; integrin beta-2 isoform X1 [KO:K06464]
118005126  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
118022291  IL15; interleukin-15 isoform X1 [KO:K05433]
118000024  TNFSF13; tumor necrosis factor ligand superfamily member 13 [KO:K05475]
118009243  TNFSF13B; tumor necrosis factor ligand superfamily member 13B [KO:K05476]
118027342  LTB; lymphotoxin-beta isoform X1 [KO:K03157]
118027255  TNF; tumor necrosis factor [KO:K03156]
118007866  IL1A; interleukin-1 alpha isoform X1 [KO:K04383]
118007867  IL1B; interleukin-1 beta [KO:K04519]
118020856  IL6; interleukin-6 [KO:K05405]
117998005  IL11; interleukin-11 [KO:K05417]
118013235  IL18; interleukin-18 isoform X1 [KO:K05482]
118022230  TLR2; toll-like receptor 2 [KO:K10159]
118022538  LOW QUALITY PROTEIN: toll-like receptor 2 [KO:K10159]
118017761  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
118019356  JUN; transcription factor AP-1 [KO:K04448]
118002212  FOS; proto-oncogene c-Fos [KO:K04379]
118022632  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
118014087  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
118002625  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
118008712  IL23A; interleukin-23 subunit alpha [KO:K05426]
118001199  IL17A; interleukin-17A [KO:K05489]
118003892  PTH; parathyroid hormone [KO:K05261]
118019025  CSF1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453]
118009176  TNFSF11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
118004720  TNFRSF11A; tumor necrosis factor receptor superfamily member 11A [KO:K05147]
118007092  ATP6V1A; V-type proton ATPase catalytic subunit A [KO:K02145] [EC:7.1.2.2]
118022062  ATP6V1B2; V-type proton ATPase subunit B, brain isoform [KO:K02147]
118007993  ATP6V1B1; V-type proton ATPase subunit B, kidney isoform [KO:K02147]
118015094  ATP6V1C1; V-type proton ATPase subunit C 1 [KO:K02148]
118007592  ATP6V1C2; V-type proton ATPase subunit C 2 isoform X1 [KO:K02148]
118002129  ATP6V1D; V-type proton ATPase subunit D [KO:K02149]
118025820  ATP6V1E1; V-type proton ATPase subunit E 1 isoform X1 [KO:K02150]
118007470  ATP6V1E2; V-type proton ATPase subunit E 2 isoform X1 [KO:K02150]
118021064  ATP6V1F; V-type proton ATPase subunit F [KO:K02151]
118017772  ATP6V1G1; V-type proton ATPase subunit G 1 [KO:K02152]
118004112  V-type proton ATPase subunit G 1-like [KO:K02152]
118027347  ATP6V1G2; V-type proton ATPase subunit G 2 [KO:K02152]
118013687  ATP6V1G3; V-type proton ATPase subunit G 3 isoform X1 [KO:K02152]
118016796  ATP6V0E1; V-type proton ATPase subunit e 1 [KO:K02153]
117998192  V-type proton ATPase subunit e 1-like [KO:K02153]
118020597  ATP6V0E2; V-type proton ATPase subunit e 2 [KO:K02153]
118016148  TCIRG1; V-type proton ATPase 116 kDa subunit a isoform X1 [KO:K02154]
118024916  ATP6V0A1; V-type proton ATPase 116 kDa subunit a isoform X1 [KO:K02154]
118018379  ATP6V0A2; V-type proton ATPase 116 kDa subunit a isoform X1 [KO:K02154]
118021138  ATP6V0A4; V-type proton ATPase 116 kDa subunit a [KO:K02154]
118014982  ATP6V0D2; V-type proton ATPase subunit d 2 [KO:K02146]
118023671  ATP6V0D1; V-type proton ATPase subunit d 1 [KO:K02146]
118014820  ATP6V1H; V-type proton ATPase subunit H isoform X1 [KO:K02144]
118014535  ATP6AP1; V-type proton ATPase subunit S1 [KO:K03662]
118021734  ATP6V0C; V-type proton ATPase 16 kDa proteolipid subunit [KO:K02155]
118019515  ATP6V0B; V-type proton ATPase 21 kDa proteolipid subunit [KO:K03661]
118000314  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
118005349  ACP5; tartrate-resistant acid phosphatase type 5 [KO:K14379] [EC:3.1.3.2]
118013155  interstitial collagenase-like [KO:K01388] [EC:3.4.24.7]
118013056  MMP3; stromelysin-1 [KO:K01394] [EC:3.4.24.17]
118023332  LOW QUALITY PROTEIN: cathepsin L1-like [KO:K01365] [EC:3.4.22.15]
118023333  cathepsin L1-like [KO:K01365] [EC:3.4.22.15]
118023348  cathepsin L1 [KO:K01365] [EC:3.4.22.15]
118017173  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
118025020  CCL5; C-C motif chemokine 5 [KO:K12499]
118024640  regakine-1-like [KO:K05408]
118024642  C-C motif chemokine 3 [KO:K05408]
118011729  CCL20; C-C motif chemokine 20 isoform X1 [KO:K14625]
118010456  C-X-C motif chemokine 6-like [KO:K05506]
118010458  CXCL8; interleukin-8 [KO:K10030]
118023063  CXCL12; stromal cell-derived factor 1 isoform X1 [KO:K10031]
118001628  VEGFA; vascular endothelial growth factor A [KO:K05448]
118009553  FLT1; vascular endothelial growth factor receptor 1 [KO:K05096] [EC:2.7.10.1]
118015118  ANGPT1; angiopoietin-1 isoform X1 [KO:K05465]
118018047  TEK; angiopoietin-1 receptor isoform X1 [KO:K05121] [EC:2.7.10.1]
118008418  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
mlx04370  VEGF signaling pathway
mlx04380  Osteoclast differentiation
mlx04620  Toll-like receptor signaling pathway
mlx04659  Th17 cell differentiation
mlx04660  T cell receptor signaling pathway
mlx04670  Leukocyte transendothelial migration
KO pathway
ko05323   
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