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

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...

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Bibliographic Details
Published in:The FEBS journal 2011-06, Vol.278 (12), p.2152-2166
Main Authors: Deng, Lu-Xia, Wu, Gui-Xia, Cao, Yue, Fan, Bo, Gao, Xiang, Luo, Lin, Huang, Ning
Format: Article
Language:English
Subjects:
acetylation
adaptive immunity
antimicrobial peptides
Base Sequence
beta-Defensins - genetics
Binding Sites - genetics
Cell Line
chromatin
epithelial cells
Gene Expression - drug effects
Gene Knockdown Techniques
high mobility group protein N2
histones
HMGN2 Protein - antagonists & inhibitors
HMGN2 Protein - genetics
HMGN2 Protein - metabolism
human β‐defensin‐2
Humans
lipopolysaccharide
lipopolysaccharides
Lipopolysaccharides - pharmacology
NF-kappa B - metabolism
p65
phosphorylation
precipitin tests
Promoter Regions, Genetic
regulation
RNA, Small Interfering - genetics
Signal Transduction
transcription factor NF-kappa B
Transcription Factor RelA - metabolism
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Summary: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.
ISSN:1742-464X
1742-4658
DOI:10.1111/j.1742-4658.2011.08132.x