title: Chaeoglobosin Fex inhibits poly(I:C)-induced activation of bone marrow-derived dendritic cells.
abstract: Dendritic cells (DCs) are implicated in the induction of autoimmune diseases and exist in lesions associated with several autoimmune inflammatory diseases. Chaeoglobosin Fex (Cha Fex), a cytochalasan-based alkaloid, was isolated from marine-derived endophytic fungus Chaetomium globosum QEN-14. In the present study, we evaluated the effect of Cha Fex on poly(I:C)-induced bone marrow-derived DCs. The results showed that Cha Fex attenuated the production of IFN-β both at the mRNA and protein level in poly(I:C)-induced DCs. Cha Fex markedly inhibited the maturation and function of the DCs with a reduced capacity to uptake antigens and low level of expression of costimulatory molecules. Moreover, Cha Fex abrogated the ability of poly(I:C)-induced DCs to promotion of T cell proliferation, Furthermore, Cha Fex inhibited the phosphorylation of IκB-α and IRF-3 in poly(I:C)-induced DCs. Cha Fex also reduced the phosphorylation of p38 and JNK, without affecting ERK1/2. These data demonstrate that that Cha Fex can exhibit an immunosuppressive effect on mouse bone marrow-derived DCs (BMDCs) via TLR3 signaling, which suggests potential application of Cha Fex in the treatment of autoimmune inflammatory diseases.
authors.affiliation: Immunology and Reproductive Biology Lab & Jiangsu Key Laboratory of Molecular Medicine, School of Medicine, Nanjing University, Nanjing 210093, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.forename: Chunyan
authors.initials: C
authors.lastname: Hua
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Yang
authors.forename: Huan
authors.initials: H
authors.lastname: Dou
authors.forename: Erguang
authors.initials: E
authors.lastname: Li
authors.forename: Renxiang
authors.initials: R
authors.lastname: Tan
authors.forename: Yayi
authors.initials: Y
authors.lastname: Hou
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D002597:Chaetomium; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D016899:Interferon-beta / Q000096:biosynthesis; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D051196:Toll-Like Receptor 3 / Q000276:immunology
chemical_list: D000470:Alkaloids; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D016899:Interferon-beta; D011070:Poly I-C