Regulation of hyaluronate production by interleukin 1 in cultured human chorionic cells.

Human chorionic cells in culture synthesized and secreted a large amount of hyaluronate as well as tissue collagenase. When these cells were treated with human recombinant interleukin 1 alpha (hrIL-1), the biosynthesis and secretion of hyaluronate were predominantly accelerated, but those of sulfated glycosaminoglycans were not modulated. This promotive effect of hrIL-1 was not due to the increase in endogenous prostaglandins including prostaglandin E2 since cyclooxygenase inhibitors, indomethacin and diclofenac did not modulate the IL-1-mediated production of hyaluronate. On the other hand, the cotreatment of chorionic cells with hrIL-1 and cycloheximide suppressed the IL-1-mediated hyaluronate production, suggesting that protein, de novo, synthesis required for the enhancement of hyaluronate synthesis. Upon treatment with hrIL-1, the membrane bound-hyaluronate synthase activity was increased up to 5-fold in a time-dependent manner. On the other hand, when chorionic cells were treated with hrIL-1 and/or protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methyl-pyperadine hydrochloride (H7), the IL-1-mediated production of hyaluronate was effectively suppressed. Similarly, H7 effectively suppressed the protein kinase activator, 12-O-tetradecanoyl-phorbol-13-acetate-enhanced production of glycosaminoglycans with a similar extent. These results indicate that IL-1-induced acceleration of hyaluronate production was reflected on the increase in hyaluronate synthase activity, and that protein kinase C participates positively in the IL-1-signal transduction for the increased synthesis of hyaluronate in human chorionic cells.