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

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

Research output: Contribution to journalArticle

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

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Epithelial Cells
Lung
Acetylation
Genetic Promoter Regions
Endotoxins
Histones
Anti-Inflammatory Agents
Glycerol Kinase
Lysophosphatidic Acid Receptors
Lysophospholipids
Airway Remodeling
MAP Kinase Signaling System
Pertussis Toxin
lysophosphatidic acid
Lysine
Culture Media
Proteins
Down-Regulation
Cell Culture Techniques
Phosphorylation

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Lysophosphatidic acid increases soluble ST2 expression in mouse lung and human bronchial epithelial cells. / Zhao, Jing; Chen, Qingyuan; Li, Hong; Myerburg, Michael; Spannhake, Ernst W; Natarajan, Viswanathan; Zhao, Yutong.

In: Cellular Signalling, Vol. 24, No. 1, 01.2012, p. 77-85.

Research output: Contribution to journalArticle

Zhao, Jing ; Chen, Qingyuan ; Li, Hong ; Myerburg, Michael ; Spannhake, Ernst W ; Natarajan, Viswanathan ; Zhao, Yutong. / Lysophosphatidic acid increases soluble ST2 expression in mouse lung and human bronchial epithelial cells. In: Cellular Signalling. 2012 ; Vol. 24, No. 1. pp. 77-85.
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