Chaetoglobosin F, a small molecule compound, possesses immunomodulatory properties on bone marrow-derived dendritic cells via TLR9 signaling pathway.
Chaetoglobosin F (Cha F), a cytochalasan-based alkaloid, was obtained from the EtOAc extract of a solid culture of Chaetomium globosum IFB-E019. Dendritic cells (DCs), the most potent antigen presenting cells, are considered as the major target in the modulation of excessive immune responses. Recognition of CpG-DNA by Toll-like receptor 9 (TLR9) on DCs is an important step in the pathogenesis of autoimmune diseases. However, the effect of Cha F on the maturation and immunostimulatory function of CpG-stimulated DCs remains unclear. This study investigated the effects of Cha F on bone marrow (BM)-derived DCs. We found that Cha F inhibits the CpG-induced DCs maturation and function by suppressing the expression of surface molecules (CD40, CD80, CD86 and MHC-II), reducing the production of cytokines and chemokines (IL-12 and CXCL-10), inhibiting the CpG-induced DCs-elicited allogeneic T-cell proliferation, and impairing the migration ability to chemokines. The Cha F-treated DCs were highly efficient at Ag capture, via mannose receptor-mediated endocytosis. Additionally, Cha F was also demonstrated to inhibit CpG-induced activation of MAPKs (p38 and JNK, but not ERK) and the nuclear translocation of NF-κB and STAT1. Furthermore, we confirmed that Cha F was able to suppress TLR9 expression of CpG-induced DCs. Collectively, these findings provide novel insight into the immunopharmacological functions of Cha F, especially with regard to their impact on CpG-induced DCs. These immunosuppressive properties of Cha F may prove useful in controlling DCs-associated autoimmune and/or inflammatory diseases.
Immunology and Reproductive Biology Lab & Jiangsu Key Laboratory of Molecular Medicine, School of Medicine, Nanjing University, Nanjing 210093, PR China.
Chunyan
C
Hua
Yonghong
Y
Yang
Lin
L
Sun
Huan
H
Dou
Renxiang
R
Tan
Yayi
Y
Hou
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002597:Chaetomium / Q000276:immunology; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D026121:Indole Alkaloids / Q000494:pharmacology*; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism*
C408982:CPG-oligonucleotide; D054357:Chemokine CXCL10; D007166:Immunosuppressive Agents; D026121:Indole Alkaloids; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9; D018664:Interleukin-12; C019290:chaetoglobosins