FGF1 alleviates LPS-induced acute lung injury via suppression of inflammation and oxidative stress

Abstract

Background Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), are devastating clinical disorders with high mortality, and for which more effective therapies are urgently needed. FGF1, the prototype member of the FGF family, is shown to exert protective effects against injurious stimuli in multiple disease models. Here we aimed to evaluate whether FGF1 pretreatment is protective against LPS-induced ALI and elucidate the potential underlying mechanisms. Methods For drug-treated groups, C57B/6 mice received a single i.p. injection of FGF1 (1 mg/kg) 1 h before the LPS challenge or not. To induce the ALI model, the mice were treated by intratracheal instillation of LPS (5 mg/kg). Then, histopathological changes in lung tissues were assessed by hematoxylin and eosin staining and transmission electron microscopy. ELISA and qPCR assays were used to detect pro-inflammatory cytokine levels in BALF and lung tissues, respectively. The total number of inflammatory cells (neutrophils and macrophages) in BALF were counted using the Wright-Giemsa method. The expressions of reactive oxygen species (ROS) and malondialdehyde (MDA) were measured using their respective kits. Western blot and immunostaining were used to evaluate the expressions of antioxidants (Nrf-2, HO-1, SOD2, GPX4, and Catalase), as well as the inflammatory and/or apoptosis-related factors (TLR4, NF-κB, and Cleaved- caspase 3). Results FGF1 pretreatment significantly ameliorated the LPS-induced histopathological changes, reduced lung wet/dry ratios, ROS and MDA levels, total BALF protein, inflammatory cell infiltration, proinflammatory cytokine levels, and significantly increased the expression of antioxidant proteins (Nrf-2, HO-1, Catalase, and SOD2). In addition, FGF1 pretreatment significantly reduced the expression of TLR4 and cleaved- caspase 3, inhibited NF-κB activation, and reduced LPS-induced cell apoptosis. Conclusions Altogether, our results suggest that FGF1 pretreatment is protective against LPS-induced ALI through mediating anti-inflammatory and antioxidant effects, which may be attributed to the downregulation of TLR4 expression and inhibition of NF-κB activation, as well as promotion of antioxidant defenses. Therefore, FGF1 administration may prove beneficial in preventative strategies for ALI/ARDS.

Canonical fibroblast growth factors in viral infection

“…In agreement with these results, systemic FGF1 treatment was found to significantly ameliorate LPS‐induced histopathological inflammatory cell infiltration and proinflammatory cytokine levels in B6 mice. In addition, FGF1 pretreatment significantly reduced LPS‐induced inflammation 62 . Again, FGF1 had a final anti‐inflammatory effect by influencing MF polarization.…”

“…In addition, FGF1 pretreatment significantly reduced LPS-induced inflammation. 62 Again, FGF1 had a final anti-inflammatory effect by influencing MF polarization. It should be noticed that downregulating the inflammatory response to LPS may be a double-edged sword: for example, local application of FGF2, applied to help healing after trauma, was shown to increase the risk of bacterial infection.…”

Heat‐KilledLactobacillus rhamnosusATCC7469 ImprovedUVB‐InducedPhotoagingViaAntiwrinkleandAntimelanogenesisImpacts

“…(34) reported that heat‐killed Lactobacillus reuteri could repress toll‐like receptor 4 (TLR4) pathway in the hearts of diabetic rats. Inhibition of TLR4 expression activated Nrf2 signaling in human endometrial epithelial cells (35) and Sirt3 signaling in mice vascular smooth muscle cells (36) and enhanced SOD2 protein expression in mice lung tissues (37). These above data suggest that RL may enhance type I collagen level and decrease mitochondrial oxidative damage relating to MAPK/AP‐1 and Nrf2/Sirt3/SOD2 signaling, respectively, thereby alleviating skin wrinkle formation.…”

Glycyrrhizic Acid Protects Experimental Sepsis Rats against Acute Lung Injury and Inflammation

“…Sepsis is a highly inflammatory disease caused by bacteria, fungi, or viruses, which leads to organ dysfunction after infection [ 1 , 2 ]. Acute respiratory distress (ARDS) is a severe form of acute lung injury (ALI) [ 3 ]. The incidence of pulmonary dysfunction and ALI/ARDS was high in sepsis aggravating morbidity and mortality [ 4 , 5 ].…”