Induction of microsomal prostaglandin E synthase-1 in human gingival fibroblasts.
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.
Yucel-Lindberg
Tülay
T
Department of Pediatric Dentistry, Institute of Odontology, Karolinska Institutet, Box 4064, S-141 04, Huddinge, Sweden. tulay.lindberg@ofa.ki.se
Hallström
Therese
T
Kats
Anna
A
Mustafa
Manal
M
Modéer
Thomas
T
D002648:Child; D004790:Enzyme Induction / Q000502:physiology; D005347:Fibroblasts / Q000201:enzymology* / Q000276:immunology; D015971:Gene Expression Regulation, Enzymologic; D005881:Gingiva / Q000166:cytology* / Q000201:enzymology* / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000235:genetics* / Q000378:metabolism*; D008861:Microsomes / Q000201:enzymology; D000071876:Prostaglandin-E Synthases; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018836:Inflammation Mediators; D012333:RNA, Messenger; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases