The chromosomal protein HMGN2 mediates lipopolysaccharide-induced expression of β-defensins in A549 cells

FEBS J. 2011 Jun;278(12):2152-66. doi: 10.1111/j.1742-4658.2011.08132.x. Epub 2011 May 18.

Abstract

Human β-defensin-2 (HBD-2) is an antimicrobial peptide produced by the epithelial cells that plays an important role in innate and adaptive immunity. Here we report that high mobility group protein N2 (HMGN2), a member of the high mobility group superfamily that affects chromatin function, modulates the expression of HBD-2 in A549 cells treated by lipopolysaccharide. Mechanistically, HMGN2 prolongs the retention time and enhances the accumulation of nuclear factor κB p65 in the nucleus, and promotes the acetylation of p65 through increasing histone acetyltransferase activity and enhancing p65-Ser536 phosphorylation. Additionally, chromatin immunoprecipitation reveals that HMGN2 and p65 synergistically promote their specific binding to HBD-2 promoter, thereby affecting the downstream transcription. Taken together, these results suggest that HMGN2 acts as a positive modulator of nuclear factor κB signalling to promote lipopolysaccharide-induced β-defensin expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding Sites / genetics
  • Cell Line
  • Gene Expression / drug effects
  • Gene Knockdown Techniques
  • HMGN2 Protein / antagonists & inhibitors
  • HMGN2 Protein / genetics
  • HMGN2 Protein / metabolism*
  • Humans
  • Lipopolysaccharides / pharmacology
  • NF-kappa B / metabolism
  • Promoter Regions, Genetic
  • RNA, Small Interfering / genetics
  • Signal Transduction
  • Transcription Factor RelA / metabolism
  • beta-Defensins / genetics*

Substances

  • DEFB4A protein, human
  • HMGN2 Protein
  • Lipopolysaccharides
  • NF-kappa B
  • RELA protein, human
  • RNA, Small Interfering
  • Transcription Factor RelA
  • beta-Defensins