Chaeoglobosin Fex inhibits poly(I:C)-induced activation of bone marrow-derived dendritic cells

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.

► Chaeoglobosin Fex, a marine derived fungal product, suppressed poly(I:C)-induced and TLR3-mediated production of pro-inflammatory mediators in bone marrow-derived DCs (BMDCs).
► The inhibitory activity of Chaeoglobosin Fex was attributed to the down-regulation of phosphorylation of JNK and p38, IκBα degradation and IRF3 activation.
► Chaeoglobosin Fex is a novel small-molecule TLR3 signaling inhibitor and could be a candidate for therapeutics of inflammatory diseases relevant to TLR3 signaling.