Divergent intracellular pathways regulate interleukin-1beta-induced miR-146a and miR-146b expression and chemokine release in human alveolar epithelial cells

FEBS Lett. 2009 Oct 20;583(20):3349-55. doi: 10.1016/j.febslet.2009.09.038. Epub 2009 Sep 26.

Abstract

We have previously reported that IL-beta-induced miR-146a and miR-146b expression negatively regulates IL-8 and RANTES release in human alveolar A549 epithelial cells. To determine the intracellular pathways that regulate this response, we demonstrate IL-1beta-induced activation of the nuclear factor (NF)-kappaB, extracellular regulated kinase (ERK)-1/2, c-jun N-terminal kinase (JNK)-1/2 and p38 mitogen activated kinase (MAP) kinase pathways. Subsequent pharmacological studies show that IL-1beta-induced miR-146a, IL-8 and RANTES production was regulated via NF-kappaB and JNK-1/2 whilst miR-146b expression was mediated via MEK-1/2 and JNK-1/2. These divergent intracellular pathways likely explain the differential expression and biological action of the miR-146 isoforms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemokine CCL5 / metabolism*
  • Enzyme Activation
  • Enzyme Inhibitors / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-8 / metabolism*
  • MAP Kinase Kinase 1 / genetics
  • MAP Kinase Kinase 1 / metabolism
  • MAP Kinase Kinase 2 / genetics
  • MAP Kinase Kinase 2 / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mitogen-Activated Protein Kinase 8 / genetics
  • Mitogen-Activated Protein Kinase 8 / metabolism
  • Mitogen-Activated Protein Kinase 9 / genetics
  • Mitogen-Activated Protein Kinase 9 / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Pulmonary Alveoli / cytology
  • Respiratory Mucosa / cytology*
  • Respiratory Mucosa / metabolism
  • Signal Transduction / physiology*
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Chemokine CCL5
  • Enzyme Inhibitors
  • Interleukin-1beta
  • Interleukin-8
  • MIRN146 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • Mitogen-Activated Protein Kinase 9
  • Extracellular Signal-Regulated MAP Kinases
  • Mitogen-Activated Protein Kinase 8
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 1
  • MAP Kinase Kinase 2