UP-REGULATION OF P21(WAF1 CIP1) IN PSORIASIS AND AFTER THE APPLICATION OF IRRITANTS AND TAPE STRIPPING/

p21(WAF1/CIP1) is a nucleoprotein that was initially characterized by its ability to be regulated transcriptionally by p53 and by its abilit y to mediate growth arrest by binding to cyclin-dependent kinases. Alt hough p21(WAF1/CIP1) is thought to mediate the effects of p53 in causi ng growth arrest, p21(WAF1/CIP1) is, also regulated in a p53-independe nt manner, e.g., during terminal differentiation of some cell lines. G rowth factors including epidermal growth factor also induce p21(WAF1/C IP1) through p53-independent pathways. Because the epidermal growth fa ctor signaling pathway is abnormal in psoriatic epidermis, we studied p21(WAF1/CIP1) expression, using in situ hybridization and immunohisto chemistry, in psoriasis. Both p21(WAF1/CIP1) mRNA and protein were sig nificantly elevated in untreated psoriatic plaques compared with uninv olved psoriatic skin (p < 0.0001), with the up-regulation of p21(WAF1/ CIP1) being predominantly suprabasal. This increase was accompanied by a small increase in p53 protein expression of uncertain significance. Furthermore, p21(WAF1/CIP1) expression was induced in skin after sell otape stripping and by the application of agents, such as dithranol, t hat are capable of inducing hyperproliferation. The pattern of p21(WAF 1/CIP1) expression observed is consistent with a role in induction and maintenance of differentiation. Our experiments, however, cannot dete rmine whether the abnormalities of p21(WAF1/CIP1) epidermal expression in psoriasis and after insult are independent of changes in p53 expre ssion.