FGF18 alleviates sepsis-induced acute lung injury by inhibiting the NF-B pathway

Background Acute lung injury (ALI) is a devastating clinical disorder with a high mortality rate, and there is an urgent need for more effective therapies. Fibroblast growth factor 18 (FGF18) has potent anti-inflammatory properties and therefore has become a focus of research for the treatment of lung injury. However, the precise role of FGF18 in the pathological process of ALI and the underlying mechanisms have not been fully elucidated. Methods A mouse model of ALI and human umbilical vein endothelial cells (HUVEC) stimulated with lipopolysaccharide (LPS) was established in vivo and in vitro. AAV-FGF18 and FGF18 proteins were used in C57BL/6J mice and HUVEC, respectively. Vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and p65 protein levels were determined by western blotting or immunofluorescent staining. Afterward, related inhibitors were used to explore the potential mechanism by which FGF18 relieves inflammation. Results In this study, we found that FGF18 was significantly upregulated in LPS-induced ALI mouse lung tissues and LPS-stimulated HUVECs. Furthermore, our studies demonstrated that overexpressing FGF18 in the lung or HUVEC could significantly alleviate LPS-induced lung injury and inhibit vascular leakage. Conclusions Mechanically, FGF18 treatment dramatically inhibited the NF-kappa B signaling pathway both in vivo and in vitro. In conclusion, these results indicate that FGF18 attenuates lung injury, at least partially, via the NF-kappa B signaling pathway and therefore may be a potential therapeutic target for ALI.