Expression of monocyte chemotactic and activating factor in rheumatoid arthritis. regulation of its production in synovial cells by interleukin‐1 and tumor necrosis factor

Abstract

Objective. To investigate whether monocyte chemotactic and activating factor (MCAF) contributes to the accumulation of macrophages in the joints of patients with rheumatoid arthritis (RA). Methods. MCAF was measured by radioimmunoassay. MCAF gene expression was determined by Northern blotting and reverse‐transcriptase polymerase chain reaction. Recombinant human MCAF was injected into rabbit joints to evaluate the effect of MCAF on infiltration of macrophages. Results. High levels of MCAF were detected in synovial fluid from patients with RA. Cells freshly isolated from synovial fluid expressed MCAF messenger RNA (mRNA). Fibroblast‐like synoviocytes were found to express MCAF mRNA and to secrete MCAF in response to interleukin‐1 (IL‐1) and tumor necrosis factor in vitro. IL‐1 also promoted MCAF gene expression in rabbit synovial tissue in vivo. MCAF caused marked infiltration of macrophages in rabbit synovial tissue. Conclusion. Our findings suggest that MCAF may contribute to the accumulation of macrophages in inflamed rheumatoid joints.

MicroRNA‐124a is a key regulator of proliferation and monocyte chemoattractant protein 1 secretion in fibroblast‐like synoviocytes from patients with rheumatoid arthritis

“…The pivotal role played by MCP-1 in RA in humans is highlighted by the findings of enhanced production of MCP-1 in serum and/or synovial fluid from patients with RA (33)(34)(35). Moreover, data from studies of animal models suggest that MCP-1 is involved in the pathogenesis of RA (36)(37)(38), and MCP-1 was recently reported to be a sensitive marker of disease activity in patients with juvenile RA (39).…”

Role of osteopontin in induction of monocyte chemoattractant protein 1 and macrophage inflammatory protein 1β through the NF‐κB and MAPK pathways in rheumatoid arthritis

“…It was reported that the levels of MCP-1 are increased in the blood, synovial fluid, and synovial tissue of patients with RA (7,8). Injection of MCP-1 into rabbit joints resulted in marked macrophage infiltration in the affected joint (8).…”

“…It was reported that the levels of MCP-1 are increased in the blood, synovial fluid, and synovial tissue of patients with RA (7,8). Injection of MCP-1 into rabbit joints resulted in marked macrophage infiltration in the affected joint (8). Treatment with MCP-1 antagonist before disease onset in an MRL/lpr mouse model of arthritis was shown to prevent the onset of arthritis (9).…”

An angiotensin receptor blocker suppresses monocyte chemoattractant protein 1 production from rheumatoid synovial fibroblasts: Comment on the article by Sagawa et al

“…Synovial tissue is the dominant source of MCP-1/CCL2 production in rheumatoid arthritis (RA), and levels of MCP-1/CCL2 are significantly increased in RA synovial tissue, synovial fluid, and peripheral blood (4). The possible role of MCP-1/CCL2 in monocyte migration toward the joint is supported by the observation that injection of MCP-1/CCL2 into the rabbit joint leads to a clear increase in macrophage numbers (5). There are several reports showing that MCP-1 is crucial for Th1 immune responses, which are important in the pathogenesis of RA as well as the CIA model (6,7).…”