Triclosan reduces microsomal prostaglandin E synthase-1 expression in human gingival fibroblasts

Objective: The effect of triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether) on the expression of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) and on the translocation of the nuclear factor-kappaB (NF-kappaB) in relation to prostaglandin E-2 (PGE(2)) production was investigated in human gingival fibroblasts challenged with tumor necrosis factor alpha (TNFalpha). Methods: Fibroblasts were established from gingival biopsies obtained from six children. COX-2 mRNA and protein expression was quantified using mRNA quantitation and enzyme immunometric assay kits. mPGES-1 mRNA was analysed by RT-PCR, mPGES-1 protein and NF-kappaB translocation by immunoblotting. PGE(2) was determined by radioimmunoassay. Results: The cytokine TNFalpha enhanced the expression of mRNA as well as the protein levels of both COX-2 and mPGES-1 and subsequently the production of PGE(2) in gingival fibroblasts. Treatment of gingival fibroblasts with triclosan (1 mug/ml) significantly reduced the stimulatory effect of TNFalpha (10 ng/ml) on the expression of mPGES-1 at both the mRNA and the protein level by an average of 21% and 43%, respectively, and subsequently the production of PGE(2) (p<0.01). Triclosan did not, however, affect the translocation of NF-kappaB or the expression of COX-2 in TNFalpha-stimulated cells. Conclusion: The results show that triclosan reduces the augmented biosynthesis of PGE(2) by inhibiting the mRNA and the protein expression of mPGES-1 in gingival fibroblasts. This finding may partly explain the anti-inflammatory effect of the agent previously reported in clinical studies.