Interleukin-1 beta induces expression of cyclooxygenase-2 mRNA 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 E2 (PGE2) 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 PGE2 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 PGE2 biosynthesis. The anti-inflammatory steroid, dexamethasone (DEX) abolished the enhanced expression of COX-2 mRNA as well as PGE2 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 PGE2 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.
Department of Orthodontics and Pediatric Dentistry Faculty of Odontology, Karolinska Institute, Huddinge, Sweden.
T
T
Yucel-Lindberg
H
H
Ahola
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S
Nilsson
J
J
Carlstedt-Duke
T
T
Modéer
D001483:Base Sequence; D002478:Cells, Cultured; D002648:Child; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D005347:Fibroblasts / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007527:Isoenzymes / Q000235:genetics*; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007375:Interleukin-1; D007527:Isoenzymes; D015335:Molecular Probes; D012333:RNA, Messenger; D003907:Dexamethasone; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate