Lysophosphatidic acid increases soluble ST2 expression in mouse lung and human bronchial epithelial cells

Jing Zhao, Qingyuan Chen, Hong Li, Michael Myerburg, Ernst Wm Spannhake, Viswanathan Natarajan, Yutong Zhao

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Lysophosphatidic acid (LPA), a naturally occurring bioactive lysophospholipid increases the expression of both pro-inflammatory and anti-inflammatory mediators in airway epithelial cells. Soluble ST2 (sST2), an anti-inflammatory mediator, has been known to function as a decoy receptor of interleukin (IL)-33 and attenuates endotoxin-induced inflammatory responses. Here, we show that LPA increased sST2 mRNA expression and protein release in a dose and time dependent manner in human bronchial epithelial cells (HBEpCs). LPA receptors antagonist and Gαi inhibitor, pertussis toxin, attenuated LPA-induced sST2 release. Inhibition of NF-κB or JNK pathway reduced LPA-induced sST2 release. LPA treatment decreased histone deacetylase 3 (HDAC3) expression and enhanced acetylation of histone H3 at lysine 9 that binds to the sST2 promoter region. Furthermore, limitation of intracellular LPA generation by the down-regulation of acetyl glycerol kinase attenuated exogenous LPA-induced histone H3 acetylation on sST2 promoter region, as well as sST2 gene expression. Treatment of HBEpCs with recombinant sST2 protein or sST2-rich cell culture media attenuated endotoxin-induced phosphorylation of PKC and airway epithelial barrier disruption. These results unravel a novel sST2 mediated signaling pathway that has physiological relevance to airway inflammation and remodeling.

Original languageEnglish (US)
Pages (from-to)77-85
Number of pages9
JournalCellular Signalling
Volume24
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

Keywords

  • Epithelial barrier function
  • Gene expression
  • Histone acetylation
  • Lysophospholipid
  • Soluble ST2

ASJC Scopus subject areas

  • Cell Biology

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