Induction of alpha(1)-antitrypsin synthesis in human articular chondrocytes by interleukin-6-type cytokines - Evidence for a local acute-phase response in the joint

Objective. We have previously shown that human articular chondrocytes synth esize large amounts of interleukin-6 (IL-6) upon stimulation with proinflam matory cytokines and that they express the IL-6 receptor. The present study was undertaken to analyze whether different IL-6-type cytokines can induce synthesis of the acute-phase protein alpha(1)-antitrypsin in human articul ar chondrocytes. Methods. Chondrocytes from human articular cartilage, cultured in agarose, were stimulated with IL-6-type cytokines. Total RNA was isolated and analyz ed by Northern blotting. Levels of alpha(1)-antitrypsin protein were determ ined by enzyme immunoassay. Results. Stimulation of chondrocytes with oncostatin M (OSM) and IL-6 led t o a 5-10-fold increase in alpha(1)-antitrypsin synthesis. This increase was dose and time dependent. Furthermore, OSM and IL-6 induced IL-6 synthesis in chondrocytes, resulting in an autocrine amplification loop. Conclusion. Our data strongly suggest the existence of a local acute-phase response in the joint. Synthesis of the acute-phase protein alpha(1)-antitr ypsin, a major inhibitor of serine proteinases, may be an important protect ive mechanism of articular chondrocytes to prevent cartilage damage in infl ammatory joint diseases.