Upregulation of tetraspanin 8 may contribute to LPSinduced acute lung injury by activation of the MAPK and NF-κB pathways

Youcai Zhu,Tian Tian,Junhua Guo,Shiping Zhu,Yongzhi Feng,Feng Tao,Xiaolong Ma

doi:10.4314/tjpr.v20i9.8

Abstract

Purpose: To investigate the effect of tetraspanin8 (Tspan8, also known as TM4SF3 or CO-029) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the related signaling pathways.Methods: Treatment with LPS was used to induce lung damage in mice and a lung epithelial cell line. The wet-to-dry weight ratio of lung tissue, hematoxylin and eosin (H&E) staining, and quantification of cytokine concentrations were conducted to validate the model. Enzyme-linked immunosorbent assays (ELISA) and quantitative polymerase chain reaction (qPCR) were used to measure levels of tumor necrosis factor alpha, interleukin (IL)-1β, and IL-6. Tspan8 levels were knocked down using shRNAs. Mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathway levels were assessed after LPS-induced injury in this cellular model.Results: Levels of Tspan8 were upregulated in the LPS-induced ALI model. Additionally, LPS treatment of mouse lung epithelial cells resulted in Tspan8 upregulation. Tspan8 knockdown alleviated the effects of LPS on lung epithelial injury by inhibiting the upregulation of MAPK and NF-κB signaling pathways.Conclusion: The upregulation of Tspan8 may promote the progression of ALI.

Highlights

Acute lung injury (ALI) involves injury to both alveolar epithelial cells and pulmonary capillary endothelial cells caused by non-cardiac factors [1]
Tetraspanin 8 (Tspan8) was upregulated in LPS-induced ALI in mice
Tspan8 protein levels significantly increased in the LPS injected group compared to controls (Figure 1D). These findings indicate that Tspan8 levels are elevated in LPSinduced ALI

Summary

Introduction

Acute lung injury (ALI) involves injury to both alveolar epithelial cells and pulmonary capillary endothelial cells caused by non-cardiac factors [1]. Pathological features of ALI include impaired alveolar capillary barriers, diffuse alveolar, and pulmonary interstitial edema [2]. The main pathophysiological features of ALI are decreased lung compliance and decreased lung volume [3]. The causes of ALI include shock, trauma, pneumonia, and other internal and. Respiratory distress and refractory hypoxemia are clinical characteristics of ALI that can worsen without intervention [2]. Despite progress in the diagnosis and treatment of ALI in recent years, the disease still has a high mortality rate of 38.5 % [3]. To improve treatment and outcomes for patients with ALI, detailed studies of its pathogenesis are needed, including the related regulatory proteins

Results

Discussion

Conclusion