Induction of microsomal prostaglandin E synthase-1 in human gingival fibroblasts

• Published in: Inflammation 2004-04, Vol.28 (2), p.89-95
• Main Authors: Yucel-Lindberg, Tülay, Hallström, Therese, Kats, Anna, Mustafa, Manal, Modéer, Thomas
• Format: Article
• Language: English
• Subjects: Child; Enzyme Induction - physiology; Fibroblasts - enzymology; Fibroblasts - immunology; Gene Expression Regulation, Enzymologic; Gingiva - cytology; Gingiva - enzymology; Gingiva - immunology; Humans; Inflammation Mediators - metabolism; Intramolecular Oxidoreductases - genetics; Intramolecular Oxidoreductases - metabolism; Microsomes - enzymology; Prostaglandin-E Synthases; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1023/B:IFLA.0000033024.13748.c1

It is well established that prostaglandin E2 (PGE2) plays an important role in inflammatory diseases including periodontitis. Previously we have reported that the inflammatory mediators interleukin-1beta, (IL-1beta) and tumor necrosis factor alpha (TNFalpha) stimulate PGE2 synthesis by inducing mRNA expression of cyclooxygenase-2 (COX-2) in human gingival fibroblasts. In present study the involvement of microsomal prostaglandin E synthase-1 (mPGES-1) in relation to PGE2 production was investigated. The results showed that IL-1beta as well as TNFalpha induced mPGES-1 mRNA and protein expression accompanied by enhanced PGE2 production in gingival fibroblasts. The anti-inflammatory steroid dexamethasone (DEX) inhibited mPGES-1 mRNA and protein expression as well as PGE2 production induced by IL-1beta or TNFalpha. The COX-2 specific inhibitor, celecoxib, in contrast to the nonspecific COX inhibitor, indomethacin, markedly reduced mPGES-1 expression induced by IL-1beta. The results demonstrate that mPGES-1 regulates PGE2 production in gingival fibroblasts stimulated by inflammatory mediators IL-1beta and TNFa. This novel pathway may be a potential target for treatment strategies of periodontal disease.