Interleukin-12 and photocarcinogenesis.
UV radiation induces immunosuppression and inflammatory responses, as well as oxidative stress and DNA damage, in skin cells and these various effects have been implicated in melanoma and nonmelanoma skin cancers, i.e., photocarcinogenesis. The cytokine interleukin (IL)-12 has been shown to possess potent antitumor activity in a wide variety of murine tumor models. In this review, we summarize the evidence that IL-12 plays a role in preventing photocarcinogenesis, and present a model of its possible mechanisms of action. Treatment of mice with IL-12 prevents UV-induced immunosuppression in a process mediated by repair of UV-induced damaged DNA. After exposure to the photocarcinogenesis protocol, the development of UV-induced tumors is more rapid and the tumor multiplicity and tumor size are significantly greater in IL-12-deficient or knockout (KO) mice than their wild-type counterparts. IL-12-deficiency in mice enhances the proliferation potential of tumor cells, and this may be one of the reasons for the rapid growth of the tumors and their greater size. The rate of malignant transformation of UV-induced papillomas to carcinomas also is higher in the IL-12 KO mice than in their wild-type counterparts in terms of carcinoma incidence and carcinoma multiplicity. UV-induced DNA damage in the form of cyclobutane pyrimidine dimers (CPDs) and sunburn cells is lower, or repaired more rapidly, in wild-type mice than IL-12 KO mice. The IL-12-associated reduction in UV-specific CPDs is due to induction of DNA repair, and particularly enhancement of nucleotide-excision repair. We suggest that endogenous stimulation of IL-12 may protect the skin from UV-induced immunosuppression, DNA damage, and, ultimately, the risk of photocarcinogenesis. Taken together, this information suggests that augmentation of IL-12 should be considered as a strategy for the prevention and treatment of photocarcinogenesis.
Katiyar
Santosh K
SK
Department of Dermatology, University of Alabama at Birmingham, 1670, University Boulevard, Volker Hall 557, P.O. Box 202, Birmingham, AL 35294, USA. skatiyar@uab.edu
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects; D012878:Skin Neoplasms / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D018664:Interleukin-12