Vasoactive intestinal peptide overexpression mediated by lentivirus attenuates lipopolysaccharide-induced acute lung injury in mice by inhibiting inflammation.

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 (Lenti-VIP) on lipopolysaccharide (LPS)-induced murine ALI. We found that the expression of intrapulmonary VIP peaked at day7 after the intratracheal injection of Lenti-VIP. Lenti-VIP increased the respiratory rate, lung compliance, and tidal volume, while decreased airway resistance in ALI mice, detected by Buxco system. Lenti-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, Lenti-VIP down-regulated pro-inflammatory tumor necrosis factor (TNF)-α 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-α 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.