MicroRNA-146 protects A549 and H1975 cells from LPS-induced apoptosis and inflammation injury

J Biosci. 2017 Dec;42(4):637-645. doi: 10.1007/s12038-017-9715-4.

Abstract

Pneumonia is an inflammatory condition affecting the lungs, in which pro-inflammatory cytokines are secreted. It has been shown that microRNA-146 (miR-146) is involved in the regulation of immune and inflammatory responses. The present study explored the protective effects of miR-146 overexpression on lipopolysaccharide (LPS)-mediated injury in A549 and H1975 cells. In this study, A549 and H1975 cells were transfected with miR-146 mimic or inhibitor, and then were subjected with LPS. Thereafter, cell viability, colony formation capacity, apoptosis, the release of proinflammatory factors, Sirt1 expression, and the expression of NF-κB and Notch pathway proteins were respectively assessed. As a result, miR- 146 overexpression exerted protective functions on LPS-damaged A549 and H1975 cells, as evidenced by the increases in cell viability and colony number, the decrease in apoptotic cell rate, as well as the down-regulations of IL-1, IL-6, and TNF-α. Sirt1 can be positively regulated by miR-146. Furthermore, miR-146 overexpression blocked NF-κB and Notch pathways, while these blocking effects were abolished when Sirt1 was silenced. The findings in the current study indicated that miR-146 protected A549 and H1975 cells from LPS-induced apoptosis and inflammation injury. miR-146 exerted protective functions might be via up-regulation of Sirt1 and thereby blocking NF-κB and Notch pathways.

MeSH terms

  • A549 Cells
  • Antagomirs / genetics
  • Antagomirs / metabolism
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Gene Expression Regulation
  • Humans
  • Interleukin-1 / antagonists & inhibitors
  • Interleukin-1 / genetics
  • Interleukin-1 / metabolism
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology*
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Molecular Mimicry
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / genetics*
  • NF-kappa B / metabolism
  • Oligonucleotides / genetics
  • Oligonucleotides / metabolism
  • Plasmids / chemistry
  • Plasmids / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Receptors, Notch / antagonists & inhibitors
  • Receptors, Notch / genetics*
  • Receptors, Notch / metabolism
  • Signal Transduction
  • Sirtuin 1 / antagonists & inhibitors
  • Sirtuin 1 / genetics*
  • Sirtuin 1 / metabolism
  • Transfection
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antagomirs
  • IL6 protein, human
  • Interleukin-1
  • Interleukin-6
  • Lipopolysaccharides
  • MIRN146 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • Oligonucleotides
  • RNA, Small Interfering
  • Receptors, Notch
  • Tumor Necrosis Factor-alpha
  • SIRT1 protein, human
  • Sirtuin 1