Phospholipase A2 Activation by Poultry Particulate Matter is Mediated Through Extracellular Signal-Regulated Kinase in Lung Epithelial Cells: Regulation of Interleukin-8 Release

Sainath R. Kotha, Melissa G. Piper, Rishi B. Patel, Sean Sliman, Smitha Malireddy, Lingying Zhao, Christopher P. Baran, Patrick S. Nana-Sinkam, Mark D. Wewers, Debra Romberger, Clay B. Marsh, Narasimham L. Parinandi

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

The mechanisms of poultry particulate matter (PM)-induced agricultural respiratory disorders are not thoroughly understood. Hence, it is hypothesized in this article that poultry PM induces the release of interleukin-8 (IL-8) by lung epithelial cells that is regulated upstream by the concerted action of cytosolic phospholipase A2 (cPLA2) and extracellular signal-regulated kinase (ERK). To test this hypothesis, the widely used cultured human lung epithelial cells (A549) were chosen as the model system. Poultry PM caused a significant activation of PLA2 in A549 cells, which was attenuated by AACOCF3 (cPLA2 inhibitor) and PD98059 (ERK-1/2 upstream inhibitor). Poultry PM induced upstream ERK-1/2 phosphorylation and downstream cPLA2 serine phosphorylation, in a concerted fashion, in cells with enhanced association of ERK-1/2 and cPLA2. The poultry PM-induced cPLA2 serine phosphorylation and IL-8 release were attenuated by AACOCF3, PD98059, and by transfection with dominant-negative ERK-1/2 DNA in cells. The poultry PM-induced IL-8 release by the bone marrow-derived macrophages of cPLA2 knockout mice was significantly lower. For the first time, this study demonstrated that the poultry PM-induced IL-8 secretion by human lung epithelial cells was regulated by cPLA2 activation through ERK-mediated serine phosphorylation, suggesting a mechanism of airway inflammation among poultry farm workers.

Original languageEnglish (US)
Pages (from-to)415-429
Number of pages15
JournalCell Biochemistry and Biophysics
Volume67
Issue number2
DOIs
StatePublished - 2013

Keywords

  • A549 cells
  • Agricultural PM
  • ERK
  • IL-8
  • Inflammatory cytokines
  • Interleukin-8
  • Lung epithelial cell
  • MAPK
  • Phospholipase A
  • Poultry dust
  • Respiratory epithelium
  • cPLA serine phosphorylation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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