Phospholipase A^sub 2^ 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; p. 415
• 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: Totowa Springer Nature B.V 01-11-2013
• Subjects: Bone marrow; Farmworkers; Occupational health; Oxidative stress; Particulate matter; Poultry farming
• ISSN: 1085-9195; 1559-0283
• DOI: 10.1007/s12013-011-9329-7

Issue Title: Special Issue: Oxidative Stress in Health and Disease; Guest Editors: Hari S. Sharma, Vijay Kumar Kutala and Periannan Kuppusamy. Also Featuring: Regular Papers 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^sub 2^ (cPLA^sub 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^sub 2^ in A549 cells, which was attenuated by AACOCF^sub 3^ (cPLA^sub 2^ inhibitor) and PD98059 (ERK-1/2 upstream inhibitor). Poultry PM induced upstream ERK-1/2 phosphorylation and downstream cPLA^sub 2^ serine phosphorylation, in a concerted fashion, in cells with enhanced association of ERK-1/2 and cPLA^sub 2^. The poultry PM-induced cPLA^sub 2^ serine phosphorylation and IL-8 release were attenuated by AACOCF^sub 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^sub 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^sub 2^ activation through ERK-mediated serine phosphorylation, suggesting a mechanism of airway inflammation among poultry farm workers.[PUBLICATION ABSTRACT]