title: Atrial natriuretic peptide suppresses Th17 development through regulation of cGMP-dependent protein kinase and PI3K-Akt signaling pathways.
abstract: In recent years, accumulating evidence suggests that atrial natriuretic peptide (ANP), a hormone widely known as a result of its significant effects on the cardiovascular system mediated by natriuretic peptide receptor A (NPRA), may play a nonnegligible role in the regulation of immune responses. In this study, we firstly investigated whether ANP signaling could regulate the differentiation and capacity of Th17 cells and discovered ANP-dose (10(-8)-10(-6)M) dependently indeed suppressed the differentiation of Th17 cells along with the reduced IL-17 production by polarizing naïve CD4(+) T cells isolated from splenocytes to Th17 phenotype in vitro. Moreover, ANP primarily signals through NPRA and cGMP-dependent protein kinase (PKG) which could be antagonized when pretreated with either ANP/NPRA signaling antagonist or PKG inhibitor. In addition, we also found that ANP signaling could upregulate the levels of phosphorylation of Akt which was hypothesized to be implicated in ANP-induced inhibition of Th17 development in our studies, and the effect of ANP on the development of murine Th17 cells seemed to be partially reversed when an inhibitor of phosphatidylinositol 3'-kinase (PI3K)/Akt had been performed in advance. Briefly, we showed for the first time that ANP signaling could suppress murine Th17 cell development from naïve CD4(+) T cells in vitro through NPRA/PKG pathway and the PI3K-Akt signal was implicated in the ANP-mediated suppression of Th17 development.
authors: Department of Respiratory Medicine, The Affiliated Hospital of Guilin Medical University, Lequn Road, No. 15, Guilin, Guangxi 541001, PR China.
authors: Libing
authors: L
authors: Ma
authors: Jinxiu
authors: J
authors: Li
authors: Guyi
authors: G
authors: Wang
authors: Subo
authors: S
authors: Gong
authors: Li
authors: L
authors: Zhang
authors: Keng
authors: K
authors: Li
authors: Xiaoying
authors: X
authors: Ji
authors: Yi
authors: Y
authors: Liu
authors: Ping
authors: P
authors: Chen
authors: Xudong
authors: X
authors: Xiang
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000276:immunology / Q000494:pharmacology; D002454:Cell Differentiation; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000276:immunology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D017461:Receptors, Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
chemical_list: D009320:Atrial Natriuretic Factor; D017869:Cyclic GMP-Dependent Protein Kinases; D020381:Interleukin-17; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A