TY - JOUR
T1 - Phospholipase A2 Activation by Poultry Particulate Matter is Mediated Through Extracellular Signal-Regulated Kinase in Lung Epithelial Cells
T2 - Regulation of Interleukin-8 Release
AU - Kotha, Sainath R.
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.
N1 - Funding Information:
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.
PY - 2013/11
Y1 - 2013/11
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.
KW - A549 cells
KW - Agricultural PM
KW - ERK
KW - IL-8
KW - Inflammatory cytokines
KW - Interleukin-8
KW - Lung epithelial cell
KW - MAPK
KW - Poultry dust
KW - Respiratory epithelium
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U2 - 10.1007/s12013-011-9329-7
DO - 10.1007/s12013-011-9329-7
M3 - Article
C2 - 22183614
AN - SCOPUS:84886589800
SN - 1085-9195
VL - 67
SP - 415
EP - 429
JO - Cell Biochemistry and Biophysics
JF - Cell Biochemistry and Biophysics
IS - 2
ER -