Protective effects of metformin on lipopolysaccharide‑induced airway epithelial cell injury via NF‑κB signaling inhibition

Sun,Jiayang; Huang,Niwen; Ma,Wen; Zhou,Haiyan; Lai,Kefang

doi:10.3892/mmr.2019.9807

Protective effects of metformin on lipopolysaccharide‑induced airway epithelial cell injury via NF‑κB signaling inhibition

Authors:
- Jiayang Sun
- Niwen Huang
- Wen Ma
- Haiyan Zhou
- Kefang Lai
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Affiliations: Department of Respiratory Medicine, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550001, P.R. China, Department of Comprehensive Ward, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550001, P.R. China, Department of Clinical Research Centre, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550001, P.R. China, Department of Clinical Research State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong 510120, P.R. China
Published online on: January 2, 2019 https://doi.org/10.3892/mmr.2019.9807
Pages: 1817-1823

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Abstract

Asthma is a heterogeneous disease characterized by chronic airway inflammation. It has been demonstrated that metformin, an extensively used drug for the treatment of type 2 diabetes, improves airway inflammation and remodeling. However, the mechanism by which this occurs remains poorly understood. The present study investigated the protective effects of metformin in lipopolysaccharide (LPS)‑induced human bronchial epithelial (16HBE) cells injury and the associated mechanisms. 16HBE cells were preincubated with metformin for 1 h and subsequently exposed to LPS for 12 h. A lactate dehydrogenase (LDH) leakage assay was used to determine the extent of injury to 16HBE cells. The expression of tumor necrosis factor‑α (TNF‑α) and interleukin‑6 (IL‑6) was measured by ELISA. The protein expression of intercellular adhesion molecule‑1 (ICAM‑1) and vascular cell adhesion molecule‑1 (VCAM‑1), as well as proteins associated with nuclear factor (NF)‑κB signaling, was measured by western blotting. Immunofluorescence assays confirmed the nuclear translocation of NF‑κB p65. The LDH leakage assays suggested that metformin significantly reduced LPS‑induced 16HBE cell injury. Furthermore, it was confirmed that metformin suppressed the LPS‑induced secretion of TNF‑α, IL‑6, ICAM‑1 and VCAM‑1. The mechanism occurred at least partially via inhibition of NF‑κB signaling. The results demonstrated that metformin inhibited NF‑κB mRNA expression and the nuclear translocation of NF‑κB p65. To the best of our knowledge, the present study was the first to demonstrate that metformin ameliorated LPS‑induced bronchial epithelial cell injury via NF‑κB signaling suppression.

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