Vasoactive intestinal peptide suppresses the NLRP3 inflammasome activation in lipopolysaccharide-induced acute lung injury mice and macrophages

Yong Zhou; Chen-Yu Zhang; Jia-Xi Duan; Qing Li; Hui-Hui Yang; Chen-Chen Sun; Jun Zhang; Xiao-Qin Luo; Shao-Kun Liu

doi:10.1016/j.biopha.2019.109596

Vasoactive intestinal peptide suppresses the NLRP3 inflammasome activation in lipopolysaccharide-induced acute lung injury mice and macrophages

Biomed Pharmacother. 2020 Jan:121:109596. doi: 10.1016/j.biopha.2019.109596. Epub 2019 Nov 12.

Authors

Yong Zhou¹, Chen-Yu Zhang¹, Jia-Xi Duan², Qing Li³, Hui-Hui Yang¹, Chen-Chen Sun¹, Jun Zhang³, Xiao-Qin Luo¹, Shao-Kun Liu⁴

Affiliations

¹ Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.
² Department of Respiratory Medicine, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China; Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan 410011, China.
³ Department of Physiology, Hunan University of Medicine, Huaihua, Hunan 418000, China.
⁴ Department of Respiratory Medicine, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China. Electronic address: shaokunliu228@csu.edu.cn.

PMID: 31731193
DOI: 10.1016/j.biopha.2019.109596

Abstract

Vasoactive intestinal peptide (VIP) is a neuropeptide that exerts anti-inflammatory functions. We have reported that VIP mediated by lentivirus attenuates acute lung injury (ALI) in lipopolysaccharide (LPS)-induced murine model. However, the exact role of VIP in uncontrolled inflammation during ALI is largely unknown. Accumulating evidence indicates that the NLRP3 inflammasome has a critical role during ALI. In this study, we investigated the effects of VIP on the activation of NLRP3 inflammasome during the development of ALI in mice. Seven days after the intratracheal injection of VIP-lentivirus, a murine ALI model was induced by intratracheal injection of LPS. VIP-lentivirus significantly reduced the expression of NLRP3 inflammasome components in lung tissue, including NLRP3, pro-caspase-1, pro-IL-1β, and pro-IL-18. VIP-lentivirus also inhibited the formation of caspase-1 p10 and the maturation of IL-1β and IL-18. In vitro, exogenous VIP pre-treatment inhibited the priming of NLRP3 inflammasome in murine primary peritoneal macrophages, indicated by down-regulation of expression of NLRP3 inflammasome components. VIP pre-treatment effectively prevented the LPS-induced degradation of I-κB and the synthesis of the downstream of NF-κB, including TNF-α and IL-17A. Furthermore, VIP pre-treatment pronouncedly suppressed the autoproteolysis of caspase-1 and the secretion of IL-1β and IL-18 induced by LPS plus ATP in macrophages. In addition, VIP inhibited the generation of reactive oxygen species in macrophages by decreasing NOX1 and NOX2 expression. These findings illustrate one mechanism that VIP attenuates ALI induced by LPS through inhibiting the activation of the NLRP3 inflammasome and encourage further studies assessing the therapeutic potential of VIP to ALI.

Keywords: NLRP3 inflammasome; acute lung injury; lipopolysaccharide; macrophages; vasoactive intestinal peptide.

MeSH terms

Acute Lung Injury / chemically induced
Acute Lung Injury / metabolism*
Acute Lung Injury / prevention & control*
Animals
Cells, Cultured
Lipopolysaccharides / toxicity*
Macrophages / drug effects
Macrophages / metabolism*
Male
Mice
NLR Family, Pyrin Domain-Containing 3 Protein / antagonists & inhibitors
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
Random Allocation
Vasoactive Intestinal Peptide / administration & dosage*

Substances

Lipopolysaccharides
NLR Family, Pyrin Domain-Containing 3 Protein
Nlrp3 protein, mouse
Vasoactive Intestinal Peptide