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

2 Citations (Scopus)

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 - Jan 1 2013

Fingerprint

Poultry
Particulate Matter
Phospholipases A2
Extracellular Signal-Regulated MAP Kinases
Cytosolic Phospholipases A2
Interleukin-8
Epithelial Cells
Chemical activation
Lung
Phosphorylation
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Serine
Time and motion study
Time and Motion Studies
Macrophages
Knockout Mice
Farms
Transfection
Bone

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

Cite this

Phospholipase A2 Activation by Poultry Particulate Matter is Mediated Through Extracellular Signal-Regulated Kinase in Lung Epithelial Cells : Regulation of Interleukin-8 Release. / Kotha, Sainath R.; Piper, Melissa G.; Patel, Rishi B.; Sliman, Sean; Malireddy, Smitha; Zhao, Lingying; Baran, Christopher P.; Nana-Sinkam, Patrick S.; Wewers, Mark D.; Romberger, Debra; Marsh, Clay B.; Parinandi, Narasimham L.

In: Cell Biochemistry and Biophysics, Vol. 67, No. 2, 01.01.2013, p. 415-429.

Research output: Contribution to journalArticle

Kotha, Sainath R. ; Piper, Melissa G. ; Patel, Rishi B. ; Sliman, Sean ; Malireddy, Smitha ; Zhao, Lingying ; Baran, Christopher P. ; Nana-Sinkam, Patrick S. ; Wewers, Mark D. ; Romberger, Debra ; Marsh, Clay B. ; Parinandi, Narasimham L. / Phospholipase A2 Activation by Poultry Particulate Matter is Mediated Through Extracellular Signal-Regulated Kinase in Lung Epithelial Cells : Regulation of Interleukin-8 Release. In: Cell Biochemistry and Biophysics. 2013 ; Vol. 67, No. 2. pp. 415-429.
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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.",
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AU - Piper, Melissa G.

AU - Patel, Rishi B.

AU - Sliman, Sean

AU - Malireddy, Smitha

AU - Zhao, Lingying

AU - Baran, Christopher P.

AU - Nana-Sinkam, Patrick S.

AU - Wewers, Mark D.

AU - Romberger, Debra

AU - Marsh, Clay B.

AU - Parinandi, Narasimham L.

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N2 - 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.

AB - 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.

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KW - Respiratory epithelium

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