title: Vasoactive intestinal peptide suppresses macrophage-mediated inflammation by downregulating interleukin-17A expression via PKA- and PKC-dependent pathways.
abstract: Interleukin (IL)-17A is a pro-inflammatory cytokine that markedly enhances inflammatory responses in the lungs by recruiting neutrophils and interacting with other pro-inflammatory mediators. Reducing the expression of IL-17A could attenuate inflammation in the lungs. However, whether VIP exerts its anti-inflammatory effects by regulating the expression of IL-17A has remained unclear. Here, we show that there is a remarkable increase of IL-17A in bronchoalveolar lavage fluid (BALF) and lung tissue of mice with acute lung injury (ALI). Moreover, lipopolysaccharides (LPS) stimulated elevated expression of IL-17A, which was evident by the enhanced levels of mRNA and protein observed. Furthermore, we also found that VIP inhibited LPS-mediated IL-17A expression in a time- and dose-dependent manner in an in vitro model of ALI and that this process might be mediated via the phosphokinase A (PKA) and phosphokinase C (PKC) pathways. Taken together, our results demonstrated that VIP might be an effective protector during ALI by suppressing IL-17A expression.
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, China.
authors.forename: Wen-Zhuo
authors.initials: WZ
authors.lastname: Ran
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, China.|Department of Anesthesiology, People's Hospital of Liuzhou City, Liuzhou, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Tang
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, China.
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Sun
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, China.
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Liu
authors.affiliation: Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, China.
authors.forename: Cha-Xiang
authors.initials: CX
authors.lastname: Guan
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000502:physiology; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
chemical_list: C098680:Il17a protein, mouse; D018836:Inflammation Mediators; D020381:Interleukin-17; D014660:Vasoactive Intestinal Peptide; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C
keywords: interleukin-17A; lipopolysaccharides; macrophages; vasoactive intestinal peptide