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

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.