Moraxella catarrhalis induces inflammatory response of bronchial epithelial cells via MAPK and NF-kappaB activation and histone deacetylase activity reduction

Am J Physiol Lung Cell Mol Physiol. 2006 May;290(5):L818-26. doi: 10.1152/ajplung.00428.2005. Epub 2006 Jan 6.

Abstract

Moraxella catarrhalis is a major cause of infectious exacerbations of chronic obstructive lung disease (COPD) and may also contribute to the pathogenesis of COPD. Little is known about M. catarrhalis-bronchial epithelium interaction. We investigated activation of M. catarrhalis infected bronchial epithelial cells and characterized the signal transduction pathways. Moreover, we tested the hypothesis that the M. catarrhalis-induced cytokine expression is regulated by acetylation of histone residues and controlled by histone deacetylase activity (HDAC). We demonstrated that M. catarrhalis induced a strong time- and dose-dependent inflammatory response in the bronchial epithelial cell line (BEAS-2B), characterized by the release of IL-8 and GM-CSF. For this cytokine liberation activation of the ERK and p38 mitogen-activated protein (MAP) kinases and transcription factor NF-kappaB was required. Furthermore, M. catarrhalis-infected bronchial epithelial cells showed an enhanced acetylation of histone H3 and H4 globally and at the promoter of the il8 gene. Preventing histone deacetylation by the histone deacetylase inhibitor trichostatin A augmented the M. catarrhalis-induced IL-8 response. After exposure to M. catarrhalis, we found a decrease in global histone deacetylase expression and activity. Our findings suggest that M. catarrhalis-induced activation of il8 gene transcription was caused by interference with epigenetic mechanisms regulating il8 gene accessibility. Our findings provide insight into important molecular and cellular mechanisms of M. catarrhalis-induced activation of human bronchial epithelium.

MeSH terms

  • Bronchi / microbiology*
  • Bronchi / physiopathology*
  • Cell Line
  • Enzyme Inhibitors / pharmacology
  • Granulocyte-Macrophage Colony-Stimulating Factor / physiology
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases / metabolism*
  • Humans
  • Inflammation / microbiology*
  • Interleukin-8 / physiology
  • Mitogen-Activated Protein Kinases / metabolism*
  • Moraxella catarrhalis / physiology*
  • NF-kappa B / metabolism*
  • Respiratory Mucosa / physiopathology*

Substances

  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Interleukin-8
  • NF-kappa B
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Mitogen-Activated Protein Kinases
  • Histone Deacetylases