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

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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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Acknowledgments

This study was supported by funds from the NIOSH (ROI OH008539), the NIH (HL40871), the Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, and Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University College of Medicine.

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Authors and Affiliations

  1. Lipid Signaling and Lipidomics Laboratory, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA

    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 & Clay B. Marsh

  2. Division of Pulmonary and Critical Care, Department of Veterans Affairs Medical Center, University of Nebraska, Omaha, NE, USA

    Debra Romberger

  3. Lipid Signaling and Lipidomics Laboratory, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Room 611-A, Columbus, OH, 43210, USA

    Narasimham L. Parinandi

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  1. Sainath R. Kotha
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  2. Melissa G. Piper
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  11. Clay B. Marsh
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  12. Narasimham L. Parinandi
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Correspondence to Narasimham L. Parinandi.

Additional information

This work is dedicated to late Dr. Val Vallyathan of NIOSH who contributed significant findings to the Occupational Health Research.

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Kotha, S.R., Piper, M.G., Patel, R.B. et al. Phospholipase A2 Activation by Poultry Particulate Matter is Mediated Through Extracellular Signal-Regulated Kinase in Lung Epithelial Cells: Regulation of Interleukin-8 Release. Cell Biochem Biophys 67, 415–429 (2013). https://doi.org/10.1007/s12013-011-9329-7

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  • DOI: https://doi.org/10.1007/s12013-011-9329-7

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