title: Silymarin inhibits ultraviolet radiation-induced immune suppression through DNA repair-dependent activation of dendritic cells and stimulation of effector T cells.
abstract: Silymarin inhibits UVB-induced immunosuppression in mouse skin. To identify the molecular mechanisms underlying this effect, 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. 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 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(+) T 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.
authors: Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors: Mudit
authors: M
authors: Vaid
authors: Ram
authors: R
authors: Prasad
authors: Tripti
authors: T
authors: Singh
authors: Craig A
authors: CA
authors: Elmets
authors: Hui
authors: H
authors: Xu
authors: Santosh K
authors: SK
authors: Katiyar
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D004260:DNA Repair; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D003877:Dermatitis, Contact / Q000517:prevention & control; D004139:Dinitrofluorobenzene; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008809:Mice, Inbred C3H; D012838:Silymarin / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D012838:Silymarin; D004139:Dinitrofluorobenzene
references: Liver Transpl. 2000 May;6(3):253-62
references: 10827224
references: Photochem Photobiol. 1996 Apr;63(4):356-7
references: 8934734
references: J Am Acad Dermatol. 1999 May;40(5 Pt 1):697-701
references: 10321596
references: Eur J Dermatol. 1999 Jun;9(4):269-75
references: 10356402
references: Cancer Res. 2008 May 15;68(10):3924-30
references: 18483278
references: Eur J Immunol. 1995 Nov;25(11):3006-10
references: 7489735
references: J Immunol. 1980 Jan;124(1):445-53
references: 6153101
references: Rev Med Interne. 1998 Apr;19(4):247-54
references: 9775150
references: J Natl Cancer Inst. 1997 Apr 16;89(8):556-66
references: 9106644
references: J Immunol. 1990 Jun 1;144(11):4121-8
references: 1971294
references: Mol Cancer Ther. 2006 Jul;5(7):1660-8
references: 16891451
references: Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2272-80
references: 16609044
references: J Heart Lung Transplant. 2000 Mar;19(3):249-55
references: 10713249
references: Prog Exp Tumor Res. 1970;13:1-27
references: 4921480
references: PLoS One. 2011;6(6):e21410
references: 21731736
references: Carcinogenesis. 2006 Jan;27(1):95-102
references: 15987716
references: Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8497-501
references: 1382291
references: Int J Oncol. 2005 Jan;26(1):169-76
references: 15586237
references: J Exp Med. 1989 Oct 1;170(4):1117-31
references: 2529340
references: Curr Protoc Immunol. 2009 Feb;Chapter 4:Unit4.9
references: 19235770
references: Cancer Prev Res (Phila). 2011 Feb;4(2):238-47
references: 21075976
references: Cancer Res. 1991 Aug 15;51(16):4176-81
references: 1678311
references: J Immunol. 1995 Oct 1;155(7):3530-7
references: 7561049
references: Int Urol Nephrol. 1999;31(4):417-22
references: 10668934
references: J Immunol. 2004 Jan 15;172(2):1036-43
references: 14707077
references: Br Med J. 1979 Dec 8;2(6203):1461-6
references: 393355
references: J Invest Dermatol. 1990 Nov;95(5):530-6
references: 2230216
references: Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7516-20
references: 1502162
references: Arzneimittelforschung. 1968 Jun;18(6):688-96
references: 5755805
references: J Immunol. 1991 Mar 15;146(6):1717-21
references: 1672330
references: J Exp Med. 1996 Mar 1;183(3):1001-12
references: 8642241
references: J Invest Dermatol. 1990 Oct;95(4):436-40
references: 2120354
references: J Exp Med. 1996 Apr 1;183(4):1491-500
references: 8666907
references: J Immunol. 2008 Mar 1;180(5):3065-71
references: 18292529
references: Proc Natl Acad Sci U S A. 1997 May 13;94(10):5255-60
references: 9144224
references: Nat Protoc. 2007;2(9):2049-56
references: 17853860
references: Cancer Prev Res (Phila). 2010 Feb;3(2):179-89
references: 20103727
references: J Invest Dermatol. 1996 May;106(5):993-1000
references: 8618064
references: J Immunol Methods. 1994 May 2;171(1):131-7
references: 8176234