Cyclophilin A may contribute to the inflammatory processes in rheumatoid arthritis through induction of matrix degrading enzymes and inflammatory cytokines from macrophages.
Cyclophilin A (CypA) levels increase in the sera and synovial fluids of rheumatoid arthritis (RA) patients, but the cell types expressing CypA and the function of CypA in the pathogenesis of RA are not known yet. Immunohistochemistry analyses revealed high level CypA staining in the macrophages in the lining layers of human RA and osteoarthritis synovium. Low level CypA staining was also detected in endothelial cells, lymphocytes, and smooth muscle cells in RA synovium. Further investigation of the CypA function using monocyte/macrophage cell lines revealed that CypA induced expression of cytokine/chemokines such as TNF-alpha, IL-8, MCP-1, and IL-1beta and matrix metalloproteinase (MMP)-9 through a pathway that is dependent on NFkappaB activation. Furthermore, MMP-9 staining pattern overlapped with that of CypA in both RA and OA synovium. Our data suggest that CypA may stimulate macrophages to degrade joint cartilage via MMP-9 expression and promote inflammation via pro-inflammatory cytokine secretion.
Kim
Ho
H
Department of Genetic Engineering, Kyungpook National University, Daegu 702-701, Republic of Korea.
Kim
Won-Jung
WJ
Jeon
Sung-Tak
ST
Koh
Eun-Mi
EM
Cha
Hoon-Suk
HS
Ahn
Kwang-Sung
KS
Lee
Won-Ha
WH
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000209:etiology / Q000276:immunology / Q000473:pathology; D002460:Cell Line; D021984:Cyclophilin A / Q000378:metabolism* / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis*; D004727:Endothelium / Q000201:enzymology / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D051379:Mice; D013583:Synovial Membrane / Q000201:enzymology / Q000276:immunology
D016207:Cytokines; D018836:Inflammation Mediators; D020780:Matrix Metalloproteinase 9; D021984:Cyclophilin A