Green tea polyphenols prevent UV-induced immunosuppression by rapid repair of DNA damage and enhancement of nucleotide excision repair genes.
UV radiation-induced immunosuppression has been implicated in the development of skin cancers. Green tea polyphenols (GTP) in drinking water prevent photocarcinogenesis in the skin of mice. We studied whether GTPs in drinking water (0.1-0.5%, w/v) prevent UV-induced immunosuppression and (if so) potential mechanisms of this effect in mice. GTPs (0.2% and 0.5%, w/v) reduced UV-induced suppression of contact hypersensitivity (CHS) in response to a contact sensitizer in local (58-62% reductions; P < 0.001) and systemic (51-55% reductions; P < 0.005) models of CHS. Compared with untreated mice, GTP-treated mice (0.2%, w/v) had a reduced number of cyclobutane pyrimidine dimer-positive (CPD(+)) cells (59%; P < 0.001) in the skin, showing faster repair of UV-induced DNA damage, and had a reduced (2-fold) migration of CPD(+) cells from the skin to draining lymph nodes, which was associated with elevated levels of nucleotide excision repair (NER) genes. GTPs did not prevent UV-induced immunosuppression in NER-deficient mice but significantly prevented it in NER-proficient mice (P < 0.001); immunohistochemical analysis of CPD(+) cells indicated that GTPs reduced the numbers of UV-induced CPD(+) cells in NER-proficient mice (P < 0.001) but not in NER-deficient mice. Southwestern dot-blot analysis revealed that GTPs repaired UV-induced CPDs in xeroderma pigmentosum complementation group A (XPA)-proficient cells of a healthy person but did not in XPA-deficient cells obtained from XPA patients, indicating that a NER mechanism is involved in DNA repair. This study is the first to show a novel NER mechanism by which drinking GTPs prevents UV-induced immunosuppression and that inhibiting UV-induced immunosuppression may underlie the chemopreventive activity of GTPs against photocarcinogenesis.
Katiyar
Santosh K
SK
Department of Dermatology, University of Alabama at Birmingham, 35294, USA. skatiyar@uab.edu
Vaid
Mudit
M
van Steeg
Harry
H
Meeran
Syed M
SM
D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D015139:Blotting, Southern; D004249:DNA Damage / Q000187:drug effects* / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects* / Q000528:radiation effects; D007150:Immunohistochemistry; D051379:Mice; D008809:Mice, Inbred C3H; D009381:Neoplasms, Radiation-Induced / Q000517:prevention & control; D010636:Phenols / Q000494:pharmacology*; D008517:Phytotherapy / Q000379:methods*; D059808:Polyphenols; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000517:prevention & control; D013662:Tea / Q000737:chemistry; D014466:Ultraviolet Rays; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics
D016588:Anticarcinogenic Agents; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D013662:Tea; D051760:Xeroderma Pigmentosum Group A Protein