Opposite regulation of the HPV20-URR and HPV27-URR promoters by ultraviolet irradiation and cytokines

Epidemiological evidence implicates ultraviolet radiation and genetic chang es (e.g., p53 mutations) as important factors in the etiology of nonmelanom a skin cancer. Little is known about a possible role of cutaneous papilloma viruses in these tumors, We previously reported both positive and negative regulation of the promoter activity of a number of HPV types by UV irradiat ion. To determine the underlying mechanism, we examined the influence of pr o-inflammatory cytokines and MAP-kinases induced by UV irradiation by trans fecting the HPV 20-URR and the HPV 27-URR into the RKO, HaCaT and H1299 cel l lines expressing wild-type or mutated p53 or lacking p53, respectively. I L-1 alpha, IL-1 beta, IL-6, IL-17, TNF-alpha, as well as interferon-alpha, -beta and -gamma activated the promoter in the HPV 20-URR but inhibited the HPV 27-URR promoter, The effect of IL-1 alpha and UV light was abolished b y the addition of IL-l receptor antagonist. UV irradiation induced a prolon ged activation of JNK in HaCaT and H 1299 but not in RKO cells, and its dep hosphorylation was enhanced in the presence of p53 and the HPV-URRs. (C) 20 01 Wiley-Liss, Inc.