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

• Published in: Cell biochemistry and biophysics Vol. 67; no. 2; pp. 415 - 429
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-11-2013
• Subjects: Biochemistry; Biological and Medical Physics; Biomedical and Life Sciences; Biophysics; Biotechnology; Cell Biology; Life Sciences; Original Paper; Pharmacology/Toxicology; Inflammatory cytokines; Agricultural PM; A549 cells; Respiratory epithelium; IL-8; MAPK; cPLA; Phospholipase A; Interleukin-8; serine phosphorylation; Lung epithelial cell; Poultry dust; ERK
• ISSN: 1085-9195; 1559-0283
• DOI: 10.1007/s12013-011-9329-7

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 A
2
(cPLA
2
) 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 PLA
2
in A549 cells, which was attenuated by AACOCF
3
(cPLA
2
inhibitor) and PD98059 (ERK-1/2 upstream inhibitor). Poultry PM induced upstream ERK-1/2 phosphorylation and downstream cPLA
2
serine phosphorylation, in a concerted fashion, in cells with enhanced association of ERK-1/2 and cPLA
2
. The poultry PM-induced cPLA
2
serine phosphorylation and IL-8 release were attenuated by AACOCF
3
, 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 cPLA
2
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 cPLA
2
activation through ERK-mediated serine phosphorylation, suggesting a mechanism of airway inflammation among poultry farm workers.