KEGG   PATHWAY: tmu05323
Entry
tmu05323                    Pathway                                
Name
Rheumatoid arthritis - Trichechus manatus latirostris (Florida manatee)
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
tmu05323  Rheumatoid arthritis
tmu05323

Organism
Trichechus manatus latirostris (Florida manatee) [GN:tmu]
Gene
101349613  T-lymphocyte activation antigen CD80 isoform X1 [KO:K05412]
101347585  T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413]
101343092  T-cell-specific surface glycoprotein CD28 isoform X1 [KO:K06470]
101351858  cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
101343312  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
101343065  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
101344101  LOW QUALITY PROTEIN: boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
101345015  boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
101361245  LOW QUALITY PROTEIN: DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
101342567  HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752]
101342817  HLA class II histocompatibility antigen, DP alpha 1 chain isoform X2 [KO:K06752]
101342571  HLA class II histocompatibility antigen, DP beta 1 chain-like [KO:K06752]
101343573  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
101345267  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
101345522  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
101348755  HLA class II histocompatibility antigen, DP alpha 1 chain-like [KO:K06752]
111819117  uncharacterized protein LOC111819117 [KO:K10784]
101361451  LOW QUALITY PROTEIN: uncharacterized protein LOC101361451 [KO:K10785]
105756611  uncharacterized protein LOC105756611 [KO:K10785]
101342429  uncharacterized protein LOC101342429 [KO:K10785]
101355641  integrin alpha-L [KO:K05718]
101349050  integrin beta-2 [KO:K06464]
101343257  intercellular adhesion molecule 1 [KO:K06490]
101341683  interleukin-15 [KO:K05433]
101354333  tumor necrosis factor ligand superfamily member 13 isoform X1 [KO:K05475]
101340999  tumor necrosis factor ligand superfamily member 13B [KO:K05476]
111820845  LOW QUALITY PROTEIN: uncharacterized protein LOC111820845 [KO:K06856]
101342909  lymphotoxin-beta isoform X1 [KO:K03157]
101342656  TNF; tumor necrosis factor [KO:K03156]
101359155  interleukin-1 alpha isoform X1 [KO:K04383]
101359415  IL1B; interleukin-1 beta [KO:K04519]
101351590  interleukin-6 [KO:K05405]
101357982  interleukin-11 isoform X2 [KO:K05417]
101348624  interleukin-18 [KO:K05482]
101342847  toll-like receptor 2 [KO:K10159]
101353470  toll-like receptor 4 [KO:K10160]
101361653  transcription factor AP-1 [KO:K04448]
101357016  proto-oncogene c-Fos [KO:K04379]
101342543  transforming growth factor beta-1 isoform X2 [KO:K13375]
101347669  transforming growth factor beta-2 isoform X1 [KO:K13376]
101358028  transforming growth factor beta-3 [KO:K13377]
101349206  interleukin-23 subunit alpha isoform X1 [KO:K05426]
101358445  interleukin-17A [KO:K05489]
101351908  parathyroid hormone [KO:K05261]
101357438  macrophage colony-stimulating factor 1 isoform X3 [KO:K05453]
101342165  tumor necrosis factor ligand superfamily member 11 [KO:K05473]
101355445  tumor necrosis factor receptor superfamily member 11A [KO:K05147]
101355338  V-type proton ATPase catalytic subunit A isoform X1 [KO:K02145] [EC:7.1.2.2]
101358707  V-type proton ATPase subunit B, kidney isoform [KO:K02147]
101346412  V-type proton ATPase subunit B, brain isoform [KO:K02147]
101349084  V-type proton ATPase subunit C 1 [KO:K02148]
101347402  V-type proton ATPase subunit C 2 [KO:K02148]
101356182  V-type proton ATPase subunit D isoform X1 [KO:K02149]
101355494  V-type proton ATPase subunit E 2 [KO:K02150]
101361881  V-type proton ATPase subunit E 1 [KO:K02150]
101345562  V-type proton ATPase subunit F [KO:K02151]
101341550  V-type proton ATPase subunit G 2 isoform X1 [KO:K02152]
101349363  LOW QUALITY PROTEIN: V-type proton ATPase subunit G 3 [KO:K02152]
101356101  V-type proton ATPase subunit G 1 [KO:K02152]
101341720  V-type proton ATPase subunit G 1-like isoform X1 [KO:K02152]
101352178  V-type proton ATPase subunit e 1 [KO:K02153]
111821627  V-type proton ATPase subunit e 2 [KO:K02153]
101341940  V-type proton ATPase 116 kDa subunit a isoform X1 [KO:K02154]
101340743  V-type proton ATPase 116 kDa subunit a [KO:K02154]
101341455  V-type proton ATPase 116 kDa subunit a isoform X1 [KO:K02154]
101348025  V-type proton ATPase 116 kDa subunit a [KO:K02154]
101349171  V-type proton ATPase subunit d 2 [KO:K02146]
101359254  V-type proton ATPase subunit d 1 isoform X1 [KO:K02146]
101347416  V-type proton ATPase subunit H isoform X4 [KO:K02144]
101345517  V-type proton ATPase subunit S1 [KO:K03662]
101360219  V-type proton ATPase 16 kDa proteolipid subunit [KO:K02155]
101359432  V-type proton ATPase 21 kDa proteolipid subunit [KO:K03661]
101349596  cathepsin K [KO:K01371] [EC:3.4.22.38]
101346745  tartrate-resistant acid phosphatase type 5 [KO:K14379] [EC:3.1.3.2]
101341516  interstitial collagenase [KO:K01388] [EC:3.4.24.7]
101341271  stromelysin-1 [KO:K01394] [EC:3.4.24.17]
101345047  cathepsin L1 [KO:K01365] [EC:3.4.22.15]
101345299  cathepsin L1-like [KO:K01365] [EC:3.4.22.15]
101342109  cathepsin L1 [KO:K01365] [EC:3.4.22.15]
101357995  granulocyte-macrophage colony-stimulating factor [KO:K05427]
101352479  C-C motif chemokine 5 [KO:K12499]
101358871  C-C motif chemokine 2 [KO:K14624]
101361964  regakine-1-like [KO:K05408]
101340657  C-C motif chemokine 3-like [KO:K05408]
101340395  C-C motif chemokine 3-like [KO:K05408]
101352919  C-C motif chemokine 20 isoform X3 [KO:K14625]
101357988  growth-regulated protein homolog gamma-like [KO:K05505]
101346678  growth-regulated alpha protein-like [KO:K05505]
101358249  C-X-C motif chemokine 6 isoform X2 [KO:K05506]
101358515  interleukin-8 [KO:K10030]
101347066  stromal cell-derived factor 1 [KO:K10031]
101341920  vascular endothelial growth factor A [KO:K05448]
101352737  vascular endothelial growth factor receptor 1 [KO:K05096] [EC:2.7.10.1]
101344008  angiopoietin-1 isoform X1 [KO:K05465]
101351895  angiopoietin-1 receptor isoform X1 [KO:K05121] [EC:2.7.10.1]
101346429  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
tmu04370  VEGF signaling pathway
tmu04380  Osteoclast differentiation
tmu04620  Toll-like receptor signaling pathway
tmu04659  Th17 cell differentiation
tmu04660  T cell receptor signaling pathway
tmu04670  Leukocyte transendothelial migration
KO pathway
ko05323   
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