Increased level of heme oxygenase-1 in rheumatoid arthritis synovial fluid.
We investigated the expression and localization of heme oxygenase-1 (HO-1) in synovial fluid and synovial tissue, and examined the stimulation of HO-1 production in rheumatoid synovial fibroblasts (RASFs). Synovial fluid samples were obtained from knee joints of 20 rheumatoid arthritis (RA) and 20 osteoarthritis (OA) patients, and concentration of HO-1 and matrix metalloproteinase-3 (MMP-3) were measured by enzyme-linked immunosorbent assay (ELISA). Synovial tissues obtained from RA or OA patients during total knee arthroplasty (TKA) were used for immunohistochemical analysis of HO-1. HO-1 production by RASFs in response to various cytokines was examined by ELISA. HO-1 levels in synovial fluid were higher in the RA group than in the OA group with significant difference (P < 0.001), and correlated with serum C-reactive protein (CRP) level (r = 0.80, P < 0.01) in the RA group. Higher levels of HO-1 were seen in the RA-L group (Larsen grade III-V) than in the RA-E (Larsen grade 0-II) group (P < 0.001). There was weak correlation between the levels of HO-1 protein and MMP-3 in synovial fluid in the RA group (r = 0.31, P < 0.01), while no positive correlation was observed in OA. Positive immunoreaction for HO-1 was observed in cells of synovial tissue including synovial fibroblasts and cells in synovial pannus. HO-1 protein levels in cultured media of RASFs were increased by stimulation by interleukin-1β at 6 h and tumor necrosis factor-alpha at 12 h, but suppressed by interferon-gamma at 12 and 24 h. These results indicated that HO-1 expression in synovial tissue might be stimulated by inflammatory cytokines. The correlation of HO-1 concentration in synovial fluid with serum CRP and MMP-3 in joint fluid indicated that HO-1 might be useful as a marker of joint inflammation in RA patients.
Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Ai
A
Kitamura
Keiichiro
K
Nishida
Takamitsu
T
Komiyama
Hideyuki
H
Doi
Yasutaka
Y
Kadota
Aki
A
Yoshida
Toshifumi
T
Ozaki
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000601:surgery; D019645:Arthroplasty, Replacement, Knee; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D004338:Drug Combinations; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000201:enzymology / Q000601:surgery; D013582:Synovial Fluid / Q000737:chemistry / Q000201:enzymology*
D015415:Biomarkers; D016207:Cytokines; D004338:Drug Combinations; D008070:Lipopolysaccharides; D051547:Heme Oxygenase-1