Dermatitis Research Today is a free monthly online journal that collates and summarizes the latest research about Dermatitis, including details on contact-, seborrheic-, atopic-, allergic-dermatitis, treatment.

Anti-inflammatory activity of sertaconazole nitrate is mediated via activation of a p38-COX-2-PGE2 pathway.

Sur R, Babad JM, Garay M, Liebel FT, Southall MD

Preclinical Pharmacology, Johnson and Johnson Skin Research Center, CPPW, a unit of Johnson & Johnson Consumer Companies, Inc., Skillman, New Jersey 08558, USA.

Sertaconazole nitrate is an antifungal agent that exhibits anti-inflammatory activity; however, the mechanism for this action was unknown. We investigated the cellular mechanisms by which sertaconazole exerts its anti-inflammatory activity in keratinocytes and human peripheral blood mononuclear cells (PBMCs). Paradoxically, sertaconazole was found to activate the proinflammatory p38 mitogen-activated protein kinase. Treatment with sertaconazole also resulted in the induction of cyclooxygenase-2 (COX-2) and the subsequent release of prostaglandin E2 (PGE2). Knocking down p38 in keratinocytes using small interfering RNA resulted in an inhibition of sertaconazole-induced PGE2 release confirming that activation of p38 was required for PGE2 production. Additionally, in stimulated keratinocytes and human PBMCs, sertaconazole was found to suppress the release of cytokines. Treatment with anti-PGE2 antiserum or the COX-2 inhibitor NS398 reversed the inhibitory effects of sertaconazole on the release of proinflammatory cytokines, linking endogenous PGE2 with the anti-inflammatory effects. Finally, in an in vivo mouse model of tetradecanoyl phorbol acetate (TPA)-induced dermatitis, the sertaconazole-mediated inhibition of TPA-induced ear edema was reversed by NS398. Biochemical analysis of tissue biopsies revealed increase in PGE2 levels in sertaconazole-treated mice. Thus, activation of the p38-COX-2-PGE2 pathway by agents such as sertaconazole provides anti-inflammatory therapeutic benefits.

Published 15 January 2008 in J Invest Dermatol, 128(2): 336-44.
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