Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

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

Youcai Zhu¹, Feng Tao², Xiaolong Ma², Junhua Guo³, Tian Tian⁴, Shiping Zhu⁵, Yongzhi Feng²

¹Department of Thoracic Disease Center, Zhejiang Rongjun Hospital, Jiaxing, Zhejiang Province 314000; ²Department of Respiratory Medicine, The First Hospital of Jiaxing (The Affiliated Hospital of Jiaxing University), Jiaxing, Zhejiang Province 314001; ³Department of Oncology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang Province, 310007; ⁴Department of Oncology, The First Affiliated Hospital of Zhejiang University Medical College, Hangzhou, Zhejiang Province 310000; ⁵Department of Respiratory and Critical Care Medicine, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang Province 310007, China.

For correspondence:- Yongzhi Feng Email: fengzhiyong_666@163.com Tel:+8657382082937

Accepted: 26 August 2021 Published: 30 September 2021

Citation: Zhu Y, Tao F, Ma X, Guo J, Tian T, Zhu S, et al. Upregulation of tetraspanin 8 may contribute to LPS-induced acute lung injury by activation of the MAPK and NF-κB pathways. Trop J Pharm Res 2021; 20(9):1833-1838 doi: 10.4314/tjpr.v20i9.8

© 2021 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

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.

Keywords: Acute lung injury (ALI), Tetraspanin 8 (Tspan8), LPS, MAPK, NF-&kappaB