Mononuclear cell-conditioned medium containing mononuclear cell factor (MCF), homologous with interleukin 1, stimulates collagen and fibronectin synthesis by adherent rheumatoid synovial cells: effects of prostaglandin E2 and indomethacin

Abstract

Adherent rheumatoid synovial cells produce and release into supernatant culture medium latent collagenase and PGE2. The levels of collagenase and PGE2 can be increased by a soluble factor present in mononuclear cell-conditioned medium, partially purified by gel-filtration, which has homologies with interleukin 1, and is produced by monocyte/macrophages. The synovial cell cultures produce collagens (procollagens) and fibronectin as well. The factor(s) present in the mononuclear cell conditioned medium which increases medium levels of collagenase PGE2 also stimulates synthesis of total protein as well as types I and III procollagen by the synovial cells. This stimulation by the monocyte factor is augmented in the presence of indomethacin, which blocks endogenous PGE2 production. Medium levels of fibronectin parallel those of procollagen. The addition of exogenous PGE2 abolishes the effect of indomethacin on collagen and fibronectin synthesis. These observations of mononuclear cell-mediated increases in fibronectin synthesis may account for the high levels of fibronectin found by others in rheumatoid synovium and synovial fluids as the increases in collagen synthesis might also explain the fibrosis observed in some rheumatoid joints.