13-Hydroxyoctadecadienoic acid reverses epidermal hyperproliferation via selective inhibition of protein kinase...

13-Hydroxyoctadecadienoic acid (13-HODE) is a major lipoxygenase metabolite of linoleic acid in epidermis. Employing a docosahexaenoic acid (22:6n-3) induced model of hyperproliferative guinea pig epidermis, we demonstrated reversal of hyperproliferation by topical 13-HODE. To delineate a possible mechanism for 13-HODE effect, we demonstrated that topical 13-HODE was incorporated into 13-HODE-containing diacylglycerol (13HODE-DAG). This novel substituted-DAG which was markedly depleted in the hyperproliferative skin paralleled the increased activities of PKC-alpha and beta. Replenishment of the hyperproliferative epidermis with topical 13-HODE resulted in the accumulation of tissue 13HODE-DAG and the selective suppression of PKC-beta activity. These data taken together suggest that the generation of putative 13-HODE-DAG and the selective suppression of PKC-beta isozyme activity may play a role in modulating epidermal hyperproliferation.