Carcinogenesis Advance Access originally published online on June 29, 2005
Carcinogenesis 2006 27(1):95-102; doi:10.1093/carcin/bgi169
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Carcinogenesis vol.27 no.1 © Oxford University Press 2005; all rights reserved.
Dietary grape-seed proanthocyanidin inhibition of ultraviolet B-induced immune suppression is associated with induction of IL-12
1 Department of Dermatology and 2 Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL, USA and 3 Birmingham VA Medical Center, Birmingham AL, USA
* To whom correspondence should be addressed at: Department of Dermatology, University of Alabama at Birmingham, 1670 University Boulevard, Volker Hall 557, PO Box 202, Birmingham, AL 35294, USA. Tel: 205 975 2608; Fax: 205 934 5745; Email: skatiyar{at}uab.edu
We have shown previously that dietary grape seed proanthocyanidins (GSPs) inhibit UVB-induced photocarcinogenesis in mice. As UVB-induced immune suppression has been implicated in the development of skin cancer risk, we investigated whether dietary GSPs can modulate the effects of UVB on the immune system. We found that the UVB-induced (180 mJ/cm2) ear swelling response (inflammatory reaction) was significantly lower in mice fed with a GSP-supplemented (0.5 and 1.0%, w/w) diet than mice fed with the standard AIN76A diet. Dietary GSPs markedly inhibited UVB-induced (180 mJ/cm2) suppression of contact hypersensitivity responses in a local model of immunosuppression but had only moderate inhibitory effect in a systemic model of immunosuppression. Dietary GSPs reduced the UVB-induced increase in immunosuppressive cytokine interleukin (IL)-10 in skin and draining lymph nodes compared with mice that did not receive GSPs. In contrast, GSPs enhanced the production of immunostimulatory cytokine IL-12 in the draining lymph nodes. Intraperitoneal injection of GSPs-fed mice with a neutralizing anti-IL-12 antibody abrogated the protective effects of the GSPs against UVB-induced suppression of the contact hypersensitivity response. These data indicate for the first time that GSPs modulate UVB-induced immunosuppression and suggest that this may be one of the possible mechanisms by which they prevent photocarcinogenesis in mice.
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