FOXA2 attenuates lipopolysaccharide‑induced pneumonia by inhibiting the inflammatory response, oxidative stress and apoptosis through blocking of p38/STAT3 signaling.

Abstract

Pneumonia is a severe inflammatory disease of the lung. Forkhead box protein A2 (FOXA2) has been demonstrated to serve an important regulatory role in various pulmonary diseases; however, the role of FOXA2 in pneumonia remains to be elucidated. The present study aimed to explore the functional effects and regulatory mechanism of FOXA2 in pneumonia. An in vitro pneumonia model was induced using lipopolysaccharide (LPS) in WI-38 cells. The mRNA and protein expression levels of FOXA2 were determined by reverse transcription-quantitative PCR and western blotting, respectively. Cell viability was assessed using a Cell Counting Kit-8 assay. Inflammatory cytokines were evaluated using ELISA kits and oxidative stress markers were assessed using a malondialdehyde assay kit, superoxide dismutase assay kit and CATalase assay kit. Cell apoptosis was evaluated using flow cytometry and the caspase3 activity was determined. Western blotting was performed to examine the protein expression levels of endoplasmic reticulum stress (ERS)-associated factors. For a rescue assay, a p38 MAPK activator, U46619, was used to investigate the regulatory mechanism of FOXA2 involving p38/STAT3 signaling. FOXA2 was downregulated in LPS-induced WI-38 cells. FOXA2 overexpression alleviated LPS-induced inflammation, oxidative stress, apoptosis and ERS in WI-38 cells. Furthermore, the inhibitory effects of FOXA2 on inflammation, oxidative stress and apoptosis, as well as ERS in LPS-induced WI-38 cells were partly weakened by additional treatment with U46619. In conclusion, FOXA2 served a protective role against LPS-induced pneumonia by regulating p38/STAT3 signaling, providing a novel idea for the development of targeted therapeutic strategies for pneumonia.