IL-1 beta-induced expression of PDGF-AA isoform in rabbit articular chondrocytes is modulated by TGF-beta 1

Abstract

Interleukin 1 beta (IL-1 beta) and platelet-derived growth factor (PDGF) induced proliferation in many cell types. Both peptides are released by activated macrophages and other cells in response to injury and are thought to play a crucial role in a number of pathological processes. We found that IL-1 beta stimulates proliferation of rabbit articular chondrocytes and induces synthesis and release of PDGF into their culture medium. This effect, which is time- and dose-dependent (0.05-5 ng/ml), is restricted to PDGF-AA, one of the three PDGF isoforms; IL-1 beta effect on PDGF is inhibited by actinomycin D and alpha-amanitin, suggesting a transcriptional regulation of PDGF-A chain. IL-1 beta stimulates PDGF-AA synthesis also in the presence of indomethacin, a prostaglandin synthesis inhibitor. Transforming growth factor beta 1 (TGF-beta 1), a dimeric polypeptide which displays multiple biological activities, inhibits in a dose-dependent manner (1-10 ng/ml) PDGF-AA production induced by IL-1 beta. In a binding assay, TGF-beta 1 induces 45% decrease in specific binding sites for 125I-IL-1 beta, with no change in affinity.