Prostaglandin E2 and I2 regulate intercellular adhesion molecule-1 expression in interleukin-1 beta-stimulated human gingival fibroblasts.

Abstract

The present study investigated the effect of prostaglandin (PG) E2 and PGI2 on intercellular adhesion molecule-1 (ICAM-1) expression in interleukin-1 beta (IL-1 beta)-stimulated human gingival fibroblasts (HGF). IL-1 beta potently induced ICAM-1 expression in HGF and indomethacin, a cyclooxygenase inhibitor, enhanced ICAM-1 expression in the cells. These data showed that endogenous PGs generated by HGF stimulated with IL-1 beta downregulated ICAM-1 expression. IL-1 beta significantly increased the levels of PGE2 and, to a lesser extent, those of 6-keto-PGF1 alpha (a stable metabolite of PGI2) in the culture media of HGF. Indomethacin completely inhibited the production of PGE2 and 6-keto-PGF1 alpha in IL-1 beta-stimulated HGF. Exogenous PGE2 and carbacyclin (a stable derivative of PGI2) in the presence of indomethacin dose-dependently suppressed ICAM-1 expression in IL-1 beta-challenged HGF. Since PGE2 and PGI2 are known to elevate intracellular cyclic AMP (cAMP) levels, we examined the effect of dibutyryl cAMP, a cAMP analogue, and isobutylmethylxanthine, a phosphodiesterase inhibitor, on ICAM-1 expression. Both agents downregulated ICAM-1 expression in IL-1 beta-stimulated HGF. These results suggest that PGE2 and PGI2 downregulate ICAM-1 expression in IL-1 beta-stimulated HGF through a cAMP-dependent mechanism and that intracellular cAMP elevation in HGF may control inflammatory and immune responses in periodontal disease.