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.
Department of dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho 2-5-1, Okayama 700-8558, Japan.
Namiko
N
Setsu
Hironori
H
Matsuura
Satoshi
S
Hirakawa
Jirô
J
Arata
Keiji
K
Iwatsuki
D002478:Cells, Cultured; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D015603:Keratinocytes / Q000201:enzymology*; D008084:Lipoxygenase / Q000096:biosynthesis*; D011565:Psoriasis / Q000201:enzymology* / Q000209:etiology*
D007371:Interferon-gamma; D008084:Lipoxygenase