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.