PPAR-gamma agonist inhibits Ang II-induced activation of dendritic cells via the MAPK and NF-kappaB pathways.
The renin-angiotensin system exerts a profound regulatory effect on the functional features of dendritic cells (DCs), thus suggesting a new target of angiotensin II (Ang II) action in the immune system. This study analyzed whether peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activation in DCs regulated Ang II-induced activation of DCs and exploited the possible molecular mechanisms, especially focused on the signaling pathways of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-kappaB). Ang II stimulation of human monocyte-derived DCs resulted in an intermediate state of DC maturation and function via modulating the balance of the negative or positive regulation of the signaling pathways of extracellular regulated kinase (ERK), p38 MAPK and NF-kappaB, but not c-Jun N-terminal kinase (JNK). Moreover, pretreatment of DCs with the PPAR-gamma agonist pioglitazone reverted these effects of Ang II on DCs via suppression of the MAPK and NF-kappaB signaling pathways at least in part. Collectively, our data support the notion that PPAR-gamma activation in human DCs inhibits the activation of DCs induced by Ang II, with which involves the regulation of MAPK and NF-kappaB signaling pathways. These findings may support the important role of these mediators in the regulation of DC-mediated inflammatory and immunologic processes.
Wei-guo
Zhu
Z
Department of Cardiology, The First Affiliated Hospital, Zhejiang University of Medicine, Hangzhou, China.
Hui
Yan
Y
Shan
Li
L
Yun
Zhang
Z
Wen-cheng
Nie
N
Fu-lin
Yu
Y
Fang-yan
Fan
F
Jun-hua
Ge
G
Jian-hua
Zhu
Z
D000804:Angiotensin II / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007249:Inflammation / Q000276:immunology; D048670:MAP Kinase Kinase 4 / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009000:Monocytes / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology*; D047495:PPAR gamma / Q000819:agonists* / Q000276:immunology; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology
D007004:Hypoglycemic Agents; D016328:NF-kappa B; D047495:PPAR gamma; D045162:Thiazolidinediones; D000804:Angiotensin II; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D000077205:Pioglitazone