Abstract 1082: Silymarin, a phytochemical from milk thistle, inhibits UVB-induced immune suppression through DNA repair-dependent activation of dendritic cells and stimulation of effector T cells .

Abstract

Abstract Ultraviolet (UV) radiation-induced immunosuppression has been implicated in the risk of skin cancers, including melanoma and non-melanoma. Topical treatment of mouse skin with silymarin, a bioactive phytochemical from milk thistle (Silybum marianum L. Gaertn.), inhibits UVB radiation-induced skin tumor development and immunosuppression in mice. To identify the molecular mechanisms underlying its effect on immune system, we used an adoptive transfer approach in which dendritic cells (DCs) from the draining lymph nodes of donor mice that had been UVB-exposed and sensitized to 2,4,-dinitrofluorobenzene (DNFB) were transferred into naïve recipient mice. The contact hypersensitivity (CHS) response of the recipient mice to DNFB was then measured. When DCs were obtained from UVB-exposed donor mice that were not treated with silymarin, the CHS response was suppressed confirming the role of DCs in the UVB-induced immunosuppression. CHS response is considered as a prototypic T-cell mediated immune response. Silymarin treatment of UVB-exposed donor mice relieved this suppression of the CHS response in the recipients. Silymarin treatment was associated with rapid repair of UVB-induced cyclobutane pyrimidine dimers (CPDs) in DCs and silymarin treatment did not prevent UV-induced immunosuppression in xeroderma pigmentosum complementation Group A (XPA)-deficient mice which are unable to repair UV-induced DNA damage. The CHS response in mice receiving DCs from silymarin-treated UV-exposed donor mice also was associated with enhanced secretion of Th1-type cytokines and stimulation of T cells. Adoptive transfer of T cells revealed that transfer of either CD8+ or CD4+ cells from silymarin-treated, UVB-exposed donors resulted in enhancement of the CHS response. Cell culture study showed enhanced secretion of IL-2 and IFNγ by CD8+ T cells, and reduced secretion of Th2 cytokines by CD4+ cells, obtained from silymarin-treated UVB-exposed mice. These data suggest that DNA repair-dependent functional activation of DCs, a reduction in CD4+ regulatory T-cell activity, and stimulation of CD8+ effector T cells contribute to silymarin-mediated inhibition of UVB-induced immunosuppression in mice. This property of silymarin can be used as an alternative strategy to augment immune system and that may help to prevent or delay the risk of skin cancers in high-risk human population. Citation Format: Mudit Vaid, Ram Prasad, Tripti Singh, Craig A. Elmets, Hui Xu, Santosh K. Katiyar. Silymarin, a phytochemical from milk thistle, inhibits UVB-induced immune suppression through DNA repair-dependent activation of dendritic cells and stimulation of effector T cells . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1082. doi:10.1158/1538-7445.AM2013-1082