Interleukin-1beta-stimulated invasion of articular cartilage by rheumatoid synovial fibroblasts is inhibited by antibodies to specific integrin receptors and by collagenase inhibitors.

Abstract

To study the role of integrin receptors in the invasion of cartilage by rheumatoid synovial fibroblasts (RSF). RSF were cocultured with cartilage slices alone or in the presence of various potential activators or inhibitors. The penetration of the cartilage surface by RSF was determined by live-cell imaging of fluorescent-labeled cells. Interleukin-1beta (IL-1beta) and IL-8 stimulated the RSF invasion of cartilage. Invasion was specific for RSF and required a concentration gradient of IL-1beta. The IL-1beta-activated invasion of cartilage was inhibited by anti-IL-1 antibodies, IL-1 receptor antagonist, and collagenase inhibitors. RSF invasion was also inhibited by antibodies to alpha4, alpha5, alphaV, and beta1 integrins. In this study, an IL-1beta concentration gradient was required for RSF invasion into cartilage, raising the possibility that in vivo invasion may be induced by IL-1beta released by chondrocytes. The IL-1beta activation of RSF assayed in vitro may contribute to the RSF invasion of cartilage in vivo. Cartilage invasion requires the availability of beta1 and alpha4, alpha5, and alphaV integrins and the presence of collagenase activity.