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Prevention of Ultraviolet Radiation–Induced Immunosuppression by (–)-Epigallocatechin-3-Gallate in Mice Is Mediated through Interleukin 12–Dependent DNA Repair

Authors' Affiliations: ¹ Department of Dermatology, University of Alabama at Birmingham and ² Birmingham Veterans Affairs Medical Center, Birmingham, Alabama

Requests for reprints: Santosh K. Katiyar, Department of Dermatology, University of Alabama at Birmingham, 1670 University Boulevard, Volker Hall 557, P.O. Box 202, Birmingham, AL 35294. Phone: 205-975-2608; Fax: 205-934-5745; E-mail: skatiyar{at}uab.edu.

Purpose: Solar UV radiation–induced immunosuppression is considered to be a risk factor for melanoma and nonmelanoma skin cancers. We previously have shown that topical application of (–)-epigallocatechin-3-gallate (EGCG) prevents UV-induced immunosuppression in mice. We studied whether prevention of UV-induced immunosuppression by EGCG is mediated through interleukin 12 (IL-12)–dependent DNA repair.

Experimental Design: IL-12 knockout (KO) mice on C3H/HeN background and DNA repair–deficient cells from xeroderma pigmentosum complementation group A (XPA) patients were used in this study. The effect of EGCG was determined on UV-induced suppression of contact hypersensitivity and UV-induced DNA damage in the form of cyclobutane pyrimidine dimers (CPD) in mice and XPA-deficient cells using immunohistochemistry and dot-blot analysis.

Results: Topical treatment with EGCG prevented UV-induced suppression of the contact hypersensitivity in wild-type (WT) mice but did not prevent it in IL-12 KO mice. Injection of anti-IL-12 monoclonal antibody to WT mice blocked the preventive effect of EGCG on UV-induced immunosuppression. EGCG reduced or repaired UV-induced DNA damage in skin faster in WT mice as shown by reduced number of CPDs⁺ cells and reduced the migration of CPD⁺ antigen-presenting cells from the skin to draining lymph nodes. In contrast, this effect of EGCG was not seen in IL-12 KO mice. Further, EGCG was able to repair UV-induced CPDs in XPA-proficient cells obtained from healthy person but did not repair in XPA-deficient cells, indicating that nucleotide excision repair mechanism is involved in DNA repair.

Conclusions: These data identify a new mechanism by which EGCG prevents UV-induced immunosuppression, and this may contribute to the chemopreventive activity of EGCG in prevention of photocarcinogenesis.

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