Vasoactive intestinal peptide overexpression mediated by lentivirus attenuates lipopolysaccharide-induced acute lung injury in mice by inhibiting inflammation
Vasoactive intestinal peptide overexpression mediated by lentivirus attenuates lipopolysaccharide-induced acute lung injury in mice by inhibiting inflammation
复制标题
慢病毒介导的血管活性肠肽过表达通过抑制炎症减轻脂多糖诱导的小鼠急性肺损伤
DOI：
10.1016/j.molimm.2018.03.002
复制
发表时间：
2018-05-01
影响因子：
3.6
通讯作者：
Guan, Cha-Xiang
中科院分区：
文献类型：
--
作者：
Sun, Guo-Ying;Yang, Hui-Hui;Guan, Cha-Xiang
血管活性肠肽（Vasoactive intestinal peptide，VIP）是肺内含量最丰富的神经肽之一，具有多种生物学特性。我们已经报道了VIP抑制TREM-1和IL-17 A的表达，其参与急性肺损伤（ALI）中炎症的启动和放大。然而，VIP对ALI的总体影响尚不清楚。本研究旨在探讨慢病毒介导的血管活性肠肽（Lend-VIP）对脂多糖（LPS）诱导的小鼠急性肺损伤（ALI）的治疗作用。我们发现肺内注射Lend-VIP后，肺内VIP的表达在第7天达到高峰。Buxco法检测Lend-VIP可增加ALI小鼠的呼吸频率、肺顺应性和潮气量，降低气道阻力。Lend-VIP显著减少炎性细胞浸润，维持肺泡隔的完整性。Lenti-VIP还能显著降低LPS诱导的ALI小鼠支气管肺泡灌洗液中总蛋白水平、中性粒细胞数量和乳酸脱氢酶活性。此外，Lend-VIP下调促炎性肿瘤坏死因子（TNF）-α mRNA和蛋白的表达，而上调抗炎性白细胞介素-10 mRNA和蛋白的表达。此外，我们观察到VIP通过蛋白激酶C和蛋白激酶A途径降低LPS刺激下小鼠巨噬细胞中TNF-α的表达。总之，我们的研究结果表明，在体内施用表达VIP的慢病毒通过抑制炎症对小鼠中LPS诱导的ALI发挥有效的治疗作用。
Vasoactive intestinal peptide (VIP) is one of the most abundant neuropeptides in the lungs with various biological characters. We have reported that VIP inhibited the expressions of TREM-1 and IL-17A, which are involved in the initiation and amplification of inflammation in acute lung injury (ALI). However, the overall effect of VIP on ALI remains unknown. The aim of this study is to investigate the therapeutic effect of VIP mediated by lentivirus (Lend-VIP) on lipopolysaccharide (LPS)-induced murine ALI. We found that the expression of intrapulmonary VIP peaked at day7 after the intratracheal injection of Lend-VIP. Lend-VIP increased the respiratory rate, lung compliance, and tidal volume, while decreased airway resistance in ALI mice, detected by Buxco system. Lend-VIP significantly reduced inflammatory cell infiltration and maintained the integrity of the alveolar septa. Lenti-VIP also remarkably decreased the total protein level, the number of neutrophil and lactate dehydrogenase activity in the bronchoalveolar lavage fluid of LPS-induced ALI mice. In addition, Lend-VIP down-regulated pro-inflammatory tumor necrosis factor (TNF)-alpha mRNA and protein expression, while up regulated anti-inflammatory interleukin-10 mRNA and protein expression in lungs of ALI mice. Furthermore, we observed that VIP reduced the TNF-alpha expression in murine macrophages under LPS stimulation through protein kinase C and protein kinase A pathways. Together, our findings show that in vivo administration of lentivirus expressing VIP exerts a potent therapeutic effect on LPS-induced ALI in mice via inhibiting inflammation.