Role of prostaglandin H synthase isoforms in murine ear edema induced by phorbol ester application on skin.
Topical application of TPA to a murine ear induced an edema that was accompanied by eicosanoid biosynthesis and an early enhancement of prostaglandin H synthase 2 (PGHS-2) expression. PGHS-2 induction may be correlated with the time-course of TPA-induced edema formation. Treatment with drugs that inhibit AA mobilization such as dexamethasone or manoalide or inhibitors of leukotriene formation such as zileuton or baicalein, reduced TPA-induced edema development and PGHS-2 levels. On the other hand, arachidonic acid (AA) application on the murine ear induced rapid expression of PGHS-2. This effect was not reproduced by other fatty acids such as oleic, linoleic, eicosatetraynoic or eicosapentaenoic acids. PGHS-2 expression induced by AA application was independent of PGHS and lipoxygenase metabolite synthesis. However, topical application of PGE2 on skin induced PGHS-2 overexpression. This study suggests that AA release and/or subsequent metabolism by PGHS may be involved in the induction of PGHS-2 expression in murine TPA- and AA-induced ear oedema.
Department of Physiological Sciences, School of Pharmacy, Barcelona University, Spain.
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Sánchez
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JJ
Moreno
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D003907:Dexamethasone / Q000494:pharmacology; D004427:Ear Diseases / Q000139:chemically induced / Q000378:metabolism*; D004487:Edema / Q000139:chemically induced / Q000378:metabolism*; D015777:Eicosanoids / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis; D012867:Skin; D013755:Tetradecanoylphorbol Acetate; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015777:Eicosanoids; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D016718:Arachidonic Acid; D003907:Dexamethasone; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D013755:Tetradecanoylphorbol Acetate