title: Silibinin polarizes Th1/Th2 immune responses through the inhibition of immunostimulatory function of dendritic cells.
abstract: Silibinin is the primary active compound in silymarin. It has been demonstrated to exert anti-carcinogenic effects and hepato-protective effects. However, the effects of silibinin on the maturation and immunostimulatory activities exhibited by dendritic cells (DCs) remain, for the most part, unknown. In this study, we have attempted to determine whether silibinin can influence surface molecule expression, dextran uptake, cytokine production, capacity to induce T-cell differentiation, and the signaling pathways underlying these phenomena in murine bone marrow-derived DCs. Silibinin was shown to significantly suppress the expression of CD80, CD86, MHC class I, and MHC class II in the DCs, and was also associated with impairments of LPS-induced IL-12 expression in the DCs. Silibinin-treated DCs proved highly efficient with regard to Ag capture via mannose receptor-mediated endocytosis. Silibinin also inhibited the LPS-induced activation of MAPKs and the nuclear translocation of the NF-kappaB p65 subunit. Additionally, silibinin-treated DCs evidenced an impaired induction of Th1 response, and a normal cell-mediated immune response. These findings provide new insight into the immunopharmacological functions of silibinin, especially with regard to their impact on the DCs. These findings expand our current understanding of the immunopharmacological functions of silibinin, and may prove useful in the development of therapeutic adjuvants for acute and chronic DC-associated diseases.
authors.affiliation: College of Pharmacy, Pusan National University, Busan, Korea.
authors.forename: Jun Sik
authors.initials: JS
authors.lastname: Lee
authors.forename: Sang Gap
authors.initials: SG
authors.lastname: Kim
authors.forename: Hyung Keun
authors.initials: HK
authors.lastname: Kim
authors.forename: Tae-Hyung
authors.initials: TH
authors.lastname: Lee
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Jeong
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Lee
authors.forename: Man-Soo
authors.initials: MS
authors.lastname: Yoon
authors.forename: Yong Jin
authors.initials: YJ
authors.lastname: Na
authors.forename: Dong-Soo
authors.initials: DS
authors.lastname: Suh
authors.forename: Nam Cheol
authors.initials: NC
authors.lastname: Park
authors.forename: In-Hak
authors.initials: IH
authors.lastname: Choi
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects* / Q000276:immunology; D000954:Antigens, Surface / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D003877:Dermatitis, Contact / Q000276:immunology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis / Q000187:drug effects / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects* / Q000276:immunology; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000494:pharmacology; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051996:Transcription Factor RelA / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D007166:Immunosuppressive Agents; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; C498144:Rela protein, mouse; D012838:Silymarin; D051996:Transcription Factor RelA; D018664:Interleukin-12; D000077385:Silybin