Pristimerin attenuates sepsis-induced lung injury by regulating nuclear factor kappaB/high-mobility group box 1 pathway

Xiao Wang,Peng Li,Lei Huang

doi:10.4314/tjpr.v19i6.7

Abstract

Purpose: To determine the effect of pristimerin on sepsis-induced lung injury, and the underlying mechanism of action.Methods: Lung injury was established in mice via induction of sepsis through cecal ligation and puncture (CLP). The effect of pristimerin was evaluated based on lung wet/dry weight and PaO2/FiO2 ratios. Lung tissue was subjected to immunohistochemical and histopathological analyses, as well as Western blotting. Furthermore, the serum levels of inflammatory mediators were determined.Results: Pristimerin reversed the altered lung wet/dry weight ratio and PaO2/FiO2 ratio in the lung, and also reduced lung injury score, relative to CLP group (p < 0.05). Moreover, it suppressed nucleocytoplasmic translocation of high mobility group protein B1 (HMGB1) in lung tissue. Serum levels of inflammatory mediators and expression levels of inducible nitric oxide synthase and nuclear factorkappaB p65 were significantly reduced by pristimerin (p < 0.05).Conclusion: Pristimerin ameliorates sepsis-induced lung injury by inhibiting HMGB1/NF-κB. Thus, this compound has a potential for clinical application in the management of lung injury. Keywords: Pristimerin, Sepsis, Lung injury, Inflammatory mediators, HMGB1

Highlights

Sepsis, a systemic inflammation due to infection, is associated with multiple organ dysfunction, and it is a leading cause of death in intensive care units [1]
Inflammation is mediated by altered expression of high-mobility group box 1 (HMGB1) which is involved in the pathogenesis of lung injury [4]
Studies have shown that nuclear factor-kappaB (NF- B) participates in the pathogenesis of lung injury by increasing the expressions of cytokines that contribute to systemic inflammation by stimulating the acetylation of the p65 subunit [7]

Summary

Introduction

A systemic inflammation due to infection, is associated with multiple organ dysfunction, and it is a leading cause of death in intensive care units [1]. Inflammation is mediated by altered expression of high-mobility group box 1 (HMGB1) which is involved in the pathogenesis of lung injury [4]. Studies have shown that NF- B participates in the pathogenesis of lung injury by increasing the expressions of cytokines that contribute to systemic inflammation by stimulating the acetylation of the p65 subunit [7].

Results

Conclusion