MicroRNA-146a modulates human bronchial epithelial cell survival in response to the cytokine-induced apoptosis

Biochem Biophys Res Commun. 2009 Feb 27;380(1):177-82. doi: 10.1016/j.bbrc.2009.01.066. Epub 2009 Jan 22.

Abstract

MicroRNA plays an important role in cell differentiation, proliferation and cell death. The current study found that miRNA-146a was up-regulated in human bronchial epithelial cells (HBECs) in response to stimulation by TGF-beta1 plus cytomix (a mixture of IL-1beta, IFN-gamma and TNF-alpha). TGF-beta1 plus cytomix (TCM) induced apoptosis in HBECs (3.4+/-0.6% of control vs 83.1+/-4.0% of TCM treated cells, p<0.01), and this was significantly blocked by the miRNA-146a mimic (8.8+/-1.5%, p<0.01). In contrast, a miRNA-146a inhibitor had only a modest effect on cell survival but appeared to augment the induction of epithelial-mesenchymal transition (EMT) in response to the cytokines. The MicroRNA-146a mimic appears to modulate HBEC survival through a mechanism of up-regulating Bcl-XL and STAT3 phosphorylation, and by this mechanism it could contribute to tissue repair and remodeling.

MeSH terms

  • Apoptosis* / genetics
  • Bronchi / cytology
  • Bronchi / drug effects
  • Bronchi / physiology*
  • Cell Survival / genetics
  • Cytokines / pharmacology
  • Cytokines / physiology*
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / physiology
  • Humans
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Phosphorylation
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / physiology*
  • STAT3 Transcription Factor / metabolism
  • bcl-X Protein / metabolism

Substances

  • BCL2L1 protein, human
  • Cytokines
  • MIRN146 microRNA, human
  • MicroRNAs
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • bcl-X Protein