Interferon-gamma-induced 15-lipoxygenase-2 expression in normal human epidermal keratinocytes and a pathogenic link to psoriasis vulgaris

Epidermal keratinocytes contain 15-lipoxygenase, which generates 15-hydroxyeicosatetraenoic acid, a major metabolite of arachidonic acid. Although two isozymes, 15-lipoxygenase-1 and -2, exist, it remains unclear which isozyme plays an important role in inflammatory processes and proliferative skin diseases. In the present study, we demonstrated that 15-lipoxygenase-2 expression was increased in normal human epidermal keratinocytes and HaCaT cells treated with interferon-gamma (200 U/ml), while no induction of 15-lipoxygenase-1 was observed. Under the same culture conditions, no 15-lipoxygenase-2 was expressed by a carcinoma cell line, A431. Weak expression of 15-lipoxygenase-2 was observed in the basal cell layer of non-lesional psoriatic skin by in situ hybridization and immunostaining, whereas strong expression of 15-lipoxygenase-2 was observed in all living layers of psoriatic lesions. Actinic keratosis and squamous cell carcinomas showed a variable immunostaining pattern for 15-lipoxygenase-2. These results indicate that 15-lipoxygenase-2 is implicated in interferon-gamma-induced inflammatory processes in normal human epidermal keratinocytes and psoriatic skin.