title: Prevention of ultraviolet radiation-induced immunosuppression by (-)-epigallocatechin-3-gallate in mice is mediated through interleukin 12-dependent DNA repair.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham and Birmingham Veterans Affairs Medical Center, Birmingham, Alabama, USA.
authors.forename: Syed M
authors.initials: SM
authors.lastname: Meeran
authors.forename: Sudheer K
authors.initials: SK
authors.lastname: Mantena
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Katiyar
mesh_terms: D000287:Administration, Topical; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D004260:DNA Repair / Q000528:radiation effects; D005838:Genotype; D006801:Humans; D007107:Immune System / Q000187:drug effects* / Q000528:radiation effects; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects; D018664:Interleukin-12 / Q000172:deficiency / Q000235:genetics / Q000528:radiation effects*; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D012680:Sensitivity and Specificity; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D016588:Anticarcinogenic Agents; D018664:Interleukin-12; D002392:Catechin; C045651:epigallocatechin gallate