rFGF4 alleviates lipopolysaccharide-induced acute lung injury by inhibiting the TLR4/NF-κB signaling pathway

• Published in: International immunopharmacology 2023-04, Vol.117, p.109923-109923, Article 109923
• Main Authors: Wang, Xianshi, Zhou, Liya, Ye, Shasha, Liu, Sidan, Chen, Lin, Cheng, Zizhao, Huang, Yuli, Wang, Beibei, Pan, Minling, Wang, Dezhong, Wang, Luhai, Lei, Zhenli, Im, Young Jun, Li, Xiaokun
• Format: Article
• Language: English
• Subjects: Acute lung injury; Acute Lung Injury - chemically induced; Acute Lung Injury - drug therapy; Acute Lung Injury - metabolism; Alveolar epithelial cells; Animals; Inflammation; Inflammation Mediators; Lipopolysaccharides; Lung - pathology; Macrophages; Mice; NF-kappa B - metabolism; Signal Transduction; TLR4; Toll-Like Receptor 4 - metabolism
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2023.109923

•rFGF4 inhibits inflammatory responses and pulmonary apoptosis in LPS-induced acute lung injury (ALI) mice.•rFGF4 inhibited the production of pro-inflammatory mediators in LPS-injured murine alveolar macrophages (MH-S) and murine pulmonary epithelial (MLE-12) cells.•rFGF4 inhibited the production of pro-inflammatory mediators in LPS-injured MH-S and MLE-12 cells through regulating the TLR4/NF-κB signaling pathway. Acute lung injury (ALI) is a serious and common clinical disease. Despite significant progress in ALI treatment, the morbidity and mortality rates remain high. However, no effective drug has been discovered for ALI. FGF4, a member of the FGF family, plays an important role in the regulation of various physiological and pathological processes. Therefore, in the present study, we aimed to study the protective effects of FGF4 against LPS-induced lung injury in vivo and in vitro. We found that rFGF4 treatment improved the lung W/D weight ratio, the survival rate, immune cell infiltration and protein concentrations in mice with LPS-induced ALI. Histological analysis revealed that rFGF4 significantly attenuated lung tissue injury and cell apoptosis. Furthermore, rFGF4 inhibited the activation of the TLR4/NF-κB signaling pathway and the production of pro-inflammatory mediators in LPS-injured lung tissues, murine alveolar macrophages (MH-S) and murine pulmonary epithelial (MLE-12) cells. The results of cell experiments further verified that rFGF4 inhibited the production of inflammatory mediators in MH-S cells and MLE-12 cells by regulating the TLR4/NF-κB signaling pathway. These results revealed that rFGF4 protected lung tissues and inhibited inflammatory mediators in mice with LPS-induced ALI by inhibiting the TLR4/NF-κB signaling pathway in MH-S and MLE-12 cells.