Granisetron protects polymicrobial sepsis-induced acute lung injury in mice

Jun Wang; Shenhai Gong; Fangzhao Wang; Mengwei Niu; Guoquan Wei; Zhanke He; Tanwei Gu; Yong Jiang; Aihua Liu; Peng Chen

doi:10.1016/j.bbrc.2018.12.031

Granisetron protects polymicrobial sepsis-induced acute lung injury in mice

Biochem Biophys Res Commun. 2019 Jan 22;508(4):1004-1010. doi: 10.1016/j.bbrc.2018.12.031. Epub 2018 Dec 11.

Authors

Jun Wang¹, Shenhai Gong², Fangzhao Wang², Mengwei Niu², Guoquan Wei², Zhanke He², Tanwei Gu², Yong Jiang³, Aihua Liu⁴, Peng Chen⁵

Affiliations

¹ Department of Respiration, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China; State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China.
² Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China; State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China.
³ Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China; State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China. Electronic address: [email protected].
⁴ Department of Respiration, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China; State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China. Electronic address: [email protected].
⁵ Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China; State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China. Electronic address: [email protected].

PMID: 30551881
DOI: 10.1016/j.bbrc.2018.12.031

Abstract

Sepsis is a serious condition with a high mortality rate worldwide. Granisetron is an anti-nausea drug for patients undergoing chemotherapy. Here we aimed to identify the novel effect of granisetron on sepsis-induced acute lung injury (ALI). Our results showed that mice treated with granisetron displayed less severe lung damage than controls. Granisetron administration reduced pulmonary neutrophil recruitment after CLP. Moreover, the expressions of Cxcl1 and Cxcl2 were diminished in the presence of granisetron in THP-1 macrophages after lipopolysaccharide exposure. Additionally, granisetron could inhibit the activation of p38 MAPK and NLRP3 inflammasome both in vivo and in vitro. Collectively, granisetron protects against sepsis-induced ALI by suppressing macrophage Cxcl1/Cxcl2 expression and neutrophil recruitment in the lung.

Keywords: ALI; Cxcl1/Cxcl2; Granisetron; Neutrophil; Nlrp3 inflammasome; Sepsis.

Publication types

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

MeSH terms

Acute Lung Injury / drug therapy*
Acute Lung Injury / microbiology*
Acute Lung Injury / pathology
Animals
Chemokine CXCL1 / metabolism
Chemokine CXCL2 / metabolism
Granisetron / pharmacology
Granisetron / therapeutic use*
Humans
Inflammasomes / metabolism
Lung / metabolism
Lung / microbiology
Lung / pathology
MAP Kinase Signaling System / drug effects
Male
Mice, Inbred C57BL
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
Neutrophil Infiltration / drug effects
Phosphorylation / drug effects
Reactive Oxygen Species / metabolism
Sepsis / drug therapy*
Sepsis / microbiology*
Sepsis / pathology
THP-1 Cells
p38 Mitogen-Activated Protein Kinases / metabolism

Substances

Chemokine CXCL1
Chemokine CXCL2
Inflammasomes
NLR Family, Pyrin Domain-Containing 3 Protein
Reactive Oxygen Species
p38 Mitogen-Activated Protein Kinases
Granisetron