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Vasoactive intestinal peptide inhibits the activation of murine fibroblasts and expression of interleukin 17 receptor C

机译:血管活性肠肽抑制鼠成纤维细胞的活化和白细胞介素17受体C的表达

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Abstract Acute respiratory distress syndrome (ARDS) is an acute, severe, and refractory pulmonary inflammation with high morbidity and mortality. Excessive activation of fibroblast during the fibroproliferative phase plays a pivotal role in the prognosis of ARDS. Our previous study demonstrated that the vasoactive intestinal peptide (VIP) is mediated by lentivirus attenuates lipopolysaccharide (LPS)‐induced ARDS in a murine model, and VIP inhibits the release of interleukin‐17A (IL‐17A) from activation macrophages. However, the effects of VIP on the activation of murine fibroblast and expression of IL‐17 receptor (IL‐17R) in ARDS remain unclear. Here, a mouse model of ARDS was established by an intratracheal injection of LPS. We found that the gene expression of col3a1 and hydroxyproline contents in the lungs were significantly increased 24?h after LPS injection. IL‐17RC rather than IL‐17RA was increased in the lungs of mice with ARDS. In vitro, LPS activated NIH3T3 cells, which was suppressed by VIP in a dose‐dependent manner. In detail, VIP reduced the hydroxyproline content and col3a1 messenger RNA induced by LPS in NIH3T3 cells, as well as the expression of α‐smooth muscle actin. Furthermore, we found that VIP inhibited the expression of IL‐17R in the lungs of mice with ARDS and NIH3T3 cells stimulated with LPS, which was partly inhibited by antagonists of protein kinase A and protein kinase C. Taken together, our results demonstrated that VIP inhibited the activation of fibroblast via downregulation of IL‐17RC, which may contribute to the protective effects of VIP against ARDS in mice.
机译:摘要急性呼吸窘迫综合征(ARDS)是一种急性,严重和难治性的肺炎,具有高发病率和死亡率。在纤维增亚纤维增液相期间的成纤维细胞过度激活在ARDS的预后起着枢转作用。我们以前的研究表明,血管活性肠肽(VIP)由慢病毒衰减脂多糖(LPS)诱导鼠模型中的ARDS,VIP抑制来自活化巨噬细胞的白细胞介素-17a(IL-17a)的释放。然而,VIP对ARDS中IL-17受体(IL-17R)的激活和IL-17受体(IL-17R)的表达的影响仍不清楚。在此,通过肿瘤内注射LPS建立了ARDS的小鼠模型。我们发现,LPS注射后,肺部中COL3A1和羟脯氨酸含量的基因表达明显增加了24μm。在用ARDS的小鼠肺部增加IL-17RC而不是IL-17RA。体外,LPS活化的NiH3T3细胞,其通过vip以剂量依赖性方式抑制。详细地,VIP通过NIH3T3细胞中的LPS诱导的羟基脯氨酸含量和COL3A1信使RNA减少,以及α-平滑肌肌动蛋白的表达。此外,我们发现VIP抑制了用LPS刺激的ARDS和NIH3T3细胞在小鼠肺中IL-17R的表达,这部分抑制了蛋白激酶A和蛋白激酶C的拮抗剂。我们的结果表明VIP通过IL-17RC的下调抑制成纤维细胞的激活,这可能有助于VIP对小鼠ARDS的保护作用。

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