Bovine lactoferrin inhibits inflammatory response and apoptosis in LPS-induced acute lung injury by targeting the PPAR-γ pathway

Abstract

Abstract Background: Lactoferrin (LF) is an iron-binding multifunctional cationic glycoprotein. Previous studies have demonstrated that LF may be a potential drug for treating acute lung injury and acute respiratory distress syndrome. In this study, we explored the anti-inflammatory effect and mechanism of bovine lactoferrin (bLF) in acute lung injury using the RNA sequencing (RNA-seq) technology and transcriptome analysis. Methods and Results: Based on the differentially expressed genes obtained from RNA-seq of the Lung from mouse model, The bioinformatics workflow was implemented using the BGISEQ-500 platform. The protein–protein interaction (PPI) network was obtained using STRING, and the hub gene was screened using Cytoscape. To verify the results of transcriptome analysis, the effects of bLF on LPS-induced BEAS-2B cells and its anti-reactive oxygen species (ROS), anti-inflammatory, and antiapoptotic effects were studied via CCK8 test, active oxygen detection test, ELISA, and western blot assay. Transcriptome analysis revealed that two hub gene modules of DEGs were screened via PPI analysis using the STRING and MCODE plug-ins of Cytoscape. Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis revealed that these core modules are enriched in the peroxisome proliferator-activated receptor (PPAR) and AMP-activated protein kinase signaling pathways. Through cell experiments, our study shows that bLF can inhibit ROS, inflammatory reaction, and LPS-induced BEAS-2B cell apoptosis, which are significantly antagonized by the PPAR-γ inhibitor GW9662, Conclusion: This study has suggested that the PPAR-γ pathway is the critical target of bLF in anti-inflammatory reactions and apoptosis of acute lung injury, which provides a direction for further research.