INTERLEUKIN-1-BETA INDUCES EXPRESSION OF CYCLOOXYGENASE-2 MESSENGER-RNA IN HUMAN GINGIVAL FIBROBLASTS

The effect of interleukin-1 beta (IL-1 beta) on the expression of cyclooxygenase-1 and -2 (COX-1 and COX-2) mRNA and its relation to prostaglandin E(2) (PGE(2)) biosynthesis in human gingival fibroblasts was studied. IL-1 beta increased levels of mRNA for COX-2 whereas the COX-1 mRNA level was unaffected. The increased COX-2 mRNA levels were accompanied by enhanced PGE(2) formation. The phorbol, 12-myristate 13-acetate (PMA), known to stimulate protein kinase C (PKC), also induced expression of COX-2 mRNA. When gingival fibroblasts were treated simultaneously with IL-1 beta and PMA, the cytokine IL-1 beta synergistically increased levels of COX-2 mRNA, accompanied by a corresponding increase in PGE(2) biosynthesis. The anti-inflammatory steroid, dexamethasone (DEX) abolished the enhanced expression of COX-2 mRNA as well as PGE(2) formation induced by IL-1 beta, PMA or the combination of IL-1 beta and PMA. The study indicates that the IL-1 beta induced PGE(2) formation is mediated by an enhanced gene expression of COX-2 in gingival fibroblasts suggesting that the enzyme COX-2 may play an important role in the regulation of prostanoid formation at inflammatory lesions in gingival tissue.