ABNORMAL BCL-2 AND TISSUE TRANSGLUTAMINASE EXPRESSION IN PSORIATIC SKIN

Cell death by apoptosis plays a key role in skin development and homeo stasis. Previous studies have shown that increased apoptosis character izes several pathologic conditions affecting human skin. Thus, the pat hogenesis of cutaneous diseases may involve an imbalance in the homeos tatic mechanisms determining whether the death of keratinocytes will o ccur by terminal differentiation or apoptosis. We investigated the inv olvement of apoptosis in psoriasis. For this purpose, we assessed, in addition to morphology and DNA fragmentation, the expression of two pu tative apoptotic genes, bcl-2 and ''tissue'' transglutaminase, in norm al and psoriatic skin. A large number of keratinocytes showing biochem ical and morphologic features of cells undergoing apoptosis was observ ed in all the suprabasal layers of the psoriatic epidermis. The plaque s from all patients analyzed showed a dramatic reduction in the number of bcl-2-positive cells localized in the basal cell compartment. In c ontrast, the psoriatic lesions presented a marked induction in ''tissu e'' transglutaminase, which was localized specifically to the cytoplas m of apoptotic keratinocytes. ''Tissue'' transglutaminase protein stai ning was undetectable in normal epidermis. The bcl-2 and ''tissue'' tr ansglutaminase staining pattern observed in psoriasis also was found i n the skin of patients affected by lichen planus. These findings indic ate that these two genes are regulated in an opposite fashion in psori atic keratinocytes undergoing apoptosis, thus confirming their antithe tic role in the cascade of events leading to the establishment of the mature apoptotic phenotype.