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

Mol Biol Rep. 2024 Apr 5;51(1):492. doi: 10.1007/s11033-024-09436-2.

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 (ALI) and acute respiratory distress syndrome (ARDS). In this study, we explored the anti-inflammatory effect and mechanism of bovine lactoferrin (bLF) in ALI using the RNA sequencing (RNA-seq) technology and transcriptome analysis.

Methods and results: Based on the differentially expressed genes (DEGs) 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 Lipopolysaccharide (LPS)-induced BEAS-2B cells and its anti-reactive oxygen species (ROS), anti-inflammatory, and antiapoptotic effects were studied via Cell Counting Kit-8 (CCK-8) 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 PPAR (peroxisome proliferator-activated receptor) and AMPK (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 ALI, which provides a direction for further research.

Keywords: Acute lung injury (ALI); Acute respiratory distress syndrome (ARDS); Bovine lactoferrin (bLF); PPAR-γ pathway; RNA-seq.

MeSH terms

  • Acute Lung Injury* / chemically induced
  • Acute Lung Injury* / drug therapy
  • Acute Lung Injury* / genetics
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Apoptosis
  • Lactoferrin* / pharmacology
  • Lipopolysaccharides
  • Mice
  • Peroxisome Proliferator-Activated Receptors / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Anti-Inflammatory Agents
  • Lactoferrin
  • Lipopolysaccharides
  • Peroxisome Proliferator-Activated Receptors
  • Reactive Oxygen Species