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

Guo-Ying Sun; Hui-Hui Yang; Xin-Xin Guan; Wen-Jing Zhong; Yong-Ping Liu; Ming-Yuan Du; Xiao-Qin Luo; Yong Zhou; Cha-Xiang Guan

doi:10.1016/j.molimm.2018.03.002

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

Mol Immunol. 2018 May:97:8-15. doi: 10.1016/j.molimm.2018.03.002. Epub 2018 Mar 12.

Authors

Guo-Ying Sun¹, Hui-Hui Yang², Xin-Xin Guan², Wen-Jing Zhong², Yong-Ping Liu², Ming-Yuan Du², Xiao-Qin Luo², Yong Zhou³, Cha-Xiang Guan⁴

Affiliations

¹ Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China; School of Medicine, Hunan Normal University, Changsha, Hunan 410013, China.
² Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.
³ Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China. Electronic address: zhouyong421@csu.edu.cn.
⁴ Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China. Electronic address: guanchaxiang@csu.edu.cn.

PMID: 29544087
DOI: 10.1016/j.molimm.2018.03.002

Abstract

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.

Keywords: Acute lung injury; Inflammation; Lentivirus; Macrophages; Vasoactive intestinal peptide.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acute Lung Injury / chemically induced
Acute Lung Injury / genetics
Acute Lung Injury / pathology
Acute Lung Injury / therapy*
Animals
Cytoprotection / genetics
Disease Models, Animal
Down-Regulation / genetics
Genetic Therapy / methods*
Genetic Vectors
Inflammation / genetics
Inflammation / prevention & control*
Lentivirus / genetics*
Lipopolysaccharides
Macrophages, Alveolar / drug effects
Macrophages, Alveolar / pathology
Male
Mice
Transfection
Vasoactive Intestinal Peptide / genetics*

Substances

Lipopolysaccharides
Vasoactive Intestinal Peptide