Luteolin alleviates LPS-induced bronchopneumonia injury in vitro and in vivo by down-regulating microRNA-132 expression

Biomed Pharmacother. 2018 Oct:106:1641-1649. doi: 10.1016/j.biopha.2018.07.094. Epub 2018 Jul 30.

Abstract

Bronchopneumonia is a common multiple infection disease under 2 years old. Luteolin is a natural flavonoid widely distributed in plants with anti-inflammatory effect. This study aimed to explore the effects of luteolin on lipopolysaccharide (LPS)-induced bronchopneumonia injury in vitro and in vivo. Firstly, the viability and apoptosis of human bronchial epithelial BEAS-2B cells after luteolin treatment were assessed. Then, cells were treated with 10 μM LPS to simulate inflammatory injury. The potential protective effects of luteolin on LPS-induced BEAS-2B cell inflammatory injury were detected. Moreover, after LPS and/or luteolin treatment, the expression of microRNA-132 (miR-132) in BEAS-2B cells was measured. The roles of miR-132 in protective activity of luteolin were investigated. Finally, the LPS-induced bronchopneumonia murine model was established and the anti-inflammatory effects of luteolin in vivo were analyzed. The results showed that LPS decreased BEAS-2B cell viability, increased cell apoptosis and enhanced inflammatory cytokines expression. Luteolin alleviated the LPS-induced viability loss, apoptosis and elevated expression of inflammatory cytokines in a dose-dependent manner. Moreover, luteolin alleviated the LPS-induced miR-132 expression increase in BEAS-2B cells. Overexpression of miR-132 reversed the protective effects of luteolin on LPS-induced inflammatory injury. Mechanistically, luteolin mitigated LPS-induced activation of NF-κB signaling pathway by down-regulation of miR-132. Furthermore, we also found that luteolin alleviated LPS-induced bronchopneumonia model in vivo. In conclusion, this study revealed that luteolin alleviated LPS-induced bronchopneumonia injury in vitro and in vivo through down-regulating miR-132. These findings provide theoretical basis for deeply exploring the treatment of bronchopneumonia in children by using luteolin.

Keywords: Bronchopneumonia; Lipopolysaccharide; Luteolin; MicroRNA-132; NF-κB signaling pathway.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Apoptosis / drug effects
  • Bronchopneumonia / chemically induced
  • Bronchopneumonia / genetics
  • Bronchopneumonia / metabolism
  • Bronchopneumonia / prevention & control*
  • Cell Line
  • Cell Survival / drug effects
  • Cytokines / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Humans
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides*
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology
  • Luteolin / pharmacology*
  • Male
  • Mice, Inbred ICR
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • NF-kappa B / metabolism
  • Signal Transduction / drug effects

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Inflammation Mediators
  • Lipopolysaccharides
  • MIRN132 microRNA, human
  • MIRN132 microRNA, mouse
  • MicroRNAs
  • NF-kappa B
  • Luteolin