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 E2 (PGE2) 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. PGE2 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 PGE2 in gingival fibroblasts. Treatment of gingival fibroblasts with triclosan (1 microg/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 PGE2 (p<0.01). Triclosan did not, however, affect the translocation of NF-kappaB or the expression of COX-2 in TNFalpha-stimulated cells.


CONCLUSIONS
The results show that triclosan reduces the augmented biosynthesis of PGE2 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.
Mustafa
M
M
Department of Pediatric Dentistry, Institute of Odontology, Huddinge, Sweden.
Wondimu
B
B
Yucel-Lindberg
T
T
Kats-Hallström
A T
AT
Jonsson
A S
AS
Modéer
T
T
D000527:Alprostadil / Q000378:metabolism*; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005881:Gingiva / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins; D008861:Microsomes / Q000201:enzymology; D016328:NF-kappa B / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014260:Triclosan / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000890:Anti-Infective Agents; D008565:Membrane Proteins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D014260:Triclosan; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000527:Alprostadil; D015232:Dinoprostone