title: PPAR-γ agonist pioglitazone regulates dendritic cells immunogenicity mediated by DC-SIGN via the MAPK and NF-κB pathways.
abstract: Dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) is a dendritic cell-specific lectin which participates in dendritic cell (DC) trafficking, antigen uptake and DC-T cell interactions at the initiation of immune responses. This study investigated whether peroxisome proliferator-activated receptor-gamma (PPAR-γ) activation in human DCs regulates the immunogenicity of DCs mediated by DC-SIGN and exploited the possible molecular mechanisms, especially focused on the signaling pathways of mitogen-activated protein kinases (MAPK) and nuclear factor-κB (NF-κB). Here, we show that the PPAR-γ agonist pioglitazone decreased DC adhesion and transmigration, and DC stimulation of T cell proliferation mediated by DC-SIGN dependent on activation of PPAR-γ, although it increased DC endocytosis independent of PPAR-γ activation. Furthermore, PPAR-γ activation by pioglitazone in DCs down-regulated the expression of DC-SIGN, which was mediated by modulating the balance of the signaling pathways of extracellular signal-regulated kinase, c-Jun N-terminal kinase and NF-κB, but not p38 MAPK. Therefore, we conclude that PPAR-γ activation in human DCs regulates the immunogenicity of DCs mediated by DC-SIGN via the pathways of MAPK and NF-κB. These findings may support the important role of these mediators in the regulation of DC-mediated inflammatory and immunologic processes.
authors: Department of Cardiology, the First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou 310003, China. Electronic address: zhuwg@zju.edu.cn.
authors: Weiguo
authors: W
authors: Zhu
authors: Department of Cardiology, the First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou 310003, China.
authors: Hui
authors: H
authors: Yan
authors: Department of Cardiology, the First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou 310003, China.
authors: Shan
authors: S
authors: Li
authors: Department of Cardiology, the First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou 310003, China.
authors: Wencheng
authors: W
authors: Nie
authors: Department of Cardiology, the First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou 310003, China.
authors: Fangyan
authors: F
authors: Fan
authors: Department of Cardiology, the First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou 310003, China. Electronic address: zhujianhua2006@hotmail.com.
authors: Jianhua
authors: J
authors: Zhu
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004705:Endocytosis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology; D045162:Thiazolidinediones / Q000494:pharmacology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D048049:Extracellular Signal-Regulated MAP Kinases; D007004:Hypoglycemic Agents; D048031:JNK Mitogen-Activated Protein Kinases; D037181:Lectins, C-Type; D016328:NF-kappa B; D047495:PPAR gamma; D000077205:Pioglitazone; D011956:Receptors, Cell Surface; D045162:Thiazolidinediones; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
keywords: DC-SIGN; Dendritic cells; Mitogen-activated protein kinases; NF-kappa B; PPAR gamma