PMID- 22739238 OWN - NLM STAT- MEDLINE DCOM- 20130719 LR - 20211203 IS - 1878-3279 (Electronic) IS - 0171-2985 (Linking) VI - 218 IP - 3 DP - 2013 Mar TI - Chaetoglobosin F, a small molecule compound, possesses immunomodulatory properties on bone marrow-derived dendritic cells via TLR9 signaling pathway. PG - 292-302 LID - S0171-2985(12)00118-0 [pii] LID - 10.1016/j.imbio.2012.05.015 [doi] AB - 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-kappaB 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. CI - Copyright (c) 2012 Elsevier GmbH. All rights reserved. FAU - Hua, Chunyan AU - Hua C AD - Immunology and Reproductive Biology Lab & Jiangsu Key Laboratory of Molecular Medicine, School of Medicine, Nanjing University, Nanjing 210093, PR China. FAU - Yang, Yonghong AU - Yang Y FAU - Sun, Lin AU - Sun L FAU - Dou, Huan AU - Dou H FAU - Tan, Renxiang AU - Tan R FAU - Hou, Yayi AU - Hou Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120523 PL - Netherlands TA - Immunobiology JT - Immunobiology JID - 8002742 RN - 0 (CPG-oligonucleotide) RN - 0 (Chemokine CXCL10) RN - 0 (Immunosuppressive Agents) RN - 0 (Indole Alkaloids) RN - 0 (NF-kappa B) RN - 0 (Oligodeoxyribonucleotides) RN - 0 (Toll-Like Receptor 9) RN - 187348-17-0 (Interleukin-12) RN - 50335-03-0 (chaetoglobosins) SB - IM MH - Animals MH - Bone Marrow Cells/immunology MH - Cell Differentiation/drug effects/immunology MH - Cells, Cultured MH - Chaetomium/immunology MH - Chemokine CXCL10/genetics/metabolism MH - Dendritic Cells/*drug effects/immunology MH - Gene Expression Regulation/drug effects/immunology MH - Immunosuppression Therapy MH - Immunosuppressive Agents/*pharmacology MH - Indole Alkaloids/*pharmacology MH - Interleukin-12/genetics/metabolism MH - Lymphocyte Activation/drug effects MH - MAP Kinase Signaling System/drug effects/immunology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - NF-kappa B/metabolism MH - Oligodeoxyribonucleotides/immunology MH - T-Lymphocytes/immunology MH - Toll-Like Receptor 9/genetics/*metabolism EDAT- 2012/06/29 06:00 MHDA- 2013/07/20 06:00 CRDT- 2012/06/29 06:00 PHST- 2012/01/14 00:00 [received] PHST- 2012/05/05 00:00 [revised] PHST- 2012/05/16 00:00 [accepted] PHST- 2012/06/29 06:00 [entrez] PHST- 2012/06/29 06:00 [pubmed] PHST- 2013/07/20 06:00 [medline] AID - S0171-2985(12)00118-0 [pii] AID - 10.1016/j.imbio.2012.05.015 [doi] PST - ppublish SO - Immunobiology. 2013 Mar;218(3):292-302. doi: 10.1016/j.imbio.2012.05.015. Epub 2012 May 23.