Psoriatic keratinocytes show reduced IRF-1 and STAT-1alpha activation in response to gamma-IFN.

Psoriasis is a chronic inflammatory dermatosis characterized by hyperproliferative keratinocytes (KC). The skin lesions are infiltrated by T cells, which secrete gamma interferon (gamma-IFN) and are believed to be necessary to maintain the psoriatic phenotype. In normal KC, gamma-IFN is a potent inhibitor of proliferation, but proliferation of KC persists in psoriatic plaques despite the presence of gamma-IFN. Immunostaining of interferon regulatory factor-1 (IRF-1) revealed that IRF-1 was localized to the basal cells of the epidermis in normal and in nonlesional psoriatic skin, but was suprabasal or completely absent in lesional psoriatic skin. This finding led to the hypothesis that abnormal signaling in the gamma-IFN pathway may occur in psoriatic KC. To test this hypothesis, we measured activation of IRF-1 and signal transducer and activator of transcription (STAT)-1alpha transcription factors in KC after stimulation with gamma-IFN. Primary cultures of KC from normal and nonlesional psoriatic skin were stimulated with gamma-IFN and subsequent transcription factor activation was measured by electrophoretic mobility shift assay. Psoriatic KC showed a reduced induction of IRF-1 and STAT-1alpha activation after stimulation with gamma-IFN, compared with normal KC. Reduced activation of IRF-1 and STAT-1alpha in response to gamma-IFN indicates a fundamental defect in the growth and differentiation control of psoriatic KC in the absence of the influence of other cell types.