Increased level of heme oxygenase-1 in rheumatoid arthritis synovial fluid

Abstract

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.

Biological links in periodontitis and rheumatoid arthritis: Discovery via text‐mining PubMed abstracts

“…HMOX1 regulates macrophage polarization and its induction can downregulate inflammatory response to LPS of periodontal pathogens . In RA synovial fluid, HMOX1 expression is raised, possibly in response to cytokines . SP1, shown as raised in both RA and periodontitis is also implicated in commensal‐induced regulatory T‐cell induction by short chain fatty acid metabolites, which may suggest its role is possibly mediated by microbial dysbiosis.…”

Impact of Oxidative Stress on Inflammation in Rheumatoid and Adjuvant Arthritis: Damage to Lipids, Proteins, and Enzymatic Antioxidant Defense in Plasma and Different Tissues

“…Several pathologic factors have been suggested to be involved in the overexpression of heme oxygenase-1 HO-1 in RA lesions. In addition to superoxides and pro-inflammatory cytokines, hypoxia may play an important role in HO-1 expression in the lesions [89,90]. AIA is an experimental model widely used to evaluate etiopathogenetic mechanisms in chronic inflammation.…”

Amelioration of human osteoarthritis symptoms with topical ‘biotherapeutics’: a phase I human trial

“…5a, b. Our previous work and those of other investigators has demonstrated a clear correlation between HO-1 activity and its effects on disease-related outcome variables in a wide range of in vitro and in vivo studies in both humans and animals (Lekli et al 2014;Clutterbuck et al 2013;Jin et al 2013;Kitamura et al 2011). …”

“…Indeed, increased activity of HO-1 in immune cells (and possibly other tissue) may account for the significant SCE treatment-associated reduction in serum CRP shown in Fig. 4 (p<0.05), as CRP level is a well-known correlate of the severity of inflammatory diseases, including OA (Jin et al 2013;Kitamura et al 2011). The relevance of increased HO-1 expression and CRP inhibition to OA and other inflammatory diseases is strengthened by earlier studies that demonstrate a close correlation between severity of joint inflammation and levels of HO-1, CRP, and matrix metalloproteinase (a tissue degradative enzyme) in synovial fluid of rheumatoid arthritis patients (Jin et al 2013;Kitamura et al 2011;Bak et al 2003).…”

“…4 (p<0.05), as CRP level is a well-known correlate of the severity of inflammatory diseases, including OA (Jin et al 2013;Kitamura et al 2011). The relevance of increased HO-1 expression and CRP inhibition to OA and other inflammatory diseases is strengthened by earlier studies that demonstrate a close correlation between severity of joint inflammation and levels of HO-1, CRP, and matrix metalloproteinase (a tissue degradative enzyme) in synovial fluid of rheumatoid arthritis patients (Jin et al 2013;Kitamura et al 2011;Bak et al 2003). These observations further underscore the role of disease-or trauma-related HO-1 expression as a general adaptive response to dysregulated inflammation with therapeutic potential in many clinical venues (Morse and Choi 2002).…”