title: Bioactive grape proanthocyanidins enhance immune reactivity in UV-irradiated skin through functional activation of dendritic cells in mice.
abstract: Ultraviolet (UV) radiation-induced immunosuppression has been implicated in skin carcinogenesis. Grape seed proanthocyanidins (GSPs) have anti-skin carcinogenic effects in mice and GSPs-fed mice exhibit a reduction in UV-induced suppression of allergic contact hypersensitivity (CHS), a prototypic T-cell-mediated response. Here, we report that dietary GSPs did not inhibit UVB-induced suppression of CHS in xeroderma pigmentosum complementation group A (XPA)-deficient mice, which lack nucleotide excision repair mechanisms. GSPs enhanced repair of UVB-induced DNA damage (cyclobutane pyrimidine dimers) in wild-type, but not XPA-deficient, dendritic cells (DC). Co-culture of CD4(+) T cells with DCs from UVB-irradiated wild-type mice resulted in suppression of T-cell proliferation and secretion of T-helper (TH) 1-type cytokines that was ameliorated when the DCs were obtained from GSP-fed mice, whereas DCs obtained from GSP-fed XPA-KO mice failed to restore T-cell proliferation. In adoptive transfer experiments, donor DCs were positively selected from the draining lymph nodes of UVB-exposed donor mice that were sensitized to 2,4,-dinitrofluorobenzene were transferred into naïve recipient mice and the CHS response assessed. Naïve recipients that received DCs from UVB-exposed wild-type donors that had been fed GSPs exhibited a full CHS response, whereas no significant CHS was observed in mice that received DCs from XPA-KO mice fed GSPs. These results suggest that GSPs prevent UVB-induced immunosuppression through DNA repair-dependent functional activation of dendritic cells in mice. Cancer Prev Res; 6(3); 242-52. ©2013 AACR.
authors: Department of Dermatology, University of Alabama at Birmingham, 1670 University Boulevard, Volker Hall 557, Birmingham, AL 35294, USA. skatiyar@uab.edu
authors: Mudit
authors: M
authors: Vaid
authors: Tripti
authors: T
authors: Singh
authors: Ram
authors: R
authors: Prasad
authors: Craig A
authors: CA
authors: Elmets
authors: Hui
authors: H
authors: Xu
authors: Santosh K
authors: SK
authors: Katiyar
mesh_terms: D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D004249:DNA Damage / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology; D005260:Female; D056604:Grape Seed Extract / Q000494:pharmacology*; D007107:Immune System / Q000187:drug effects / Q000528:radiation effects; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D044945:Proanthocyanidins / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D027843:Vitis / Q000737:chemistry
chemical_list: D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D044945:Proanthocyanidins