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Vasoactive intestinal peptide suppresses macrophage‐mediated inflammation by downregulating interleukin‐17A expression via PKA‐ and PKC‐dependent pathways
Authors:Wen‐Zhuo Ran  Liang Dong  Chun‐Yan Tang  Yong Zhou  Guo‐Ying Sun  Tian Liu  Yong‐Ping Liu  Cha‐Xiang Guan
Affiliation:1. Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, China;2. Department of Anesthesiology, People's Hospital of Liuzhou City, Liuzhou, China
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.
Keywords:interleukin‐17A  lipopolysaccharides  macrophages  vasoactive intestinal peptide
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