Phospholipase A(2) activation by poultry particulate matter is mediated through extracellular signal-regulated kinase in lung epithelial cells: regulation of interleukin-8 release.
Kotha SR; Piper MG; Patel RB; Sliman S; Malireddy S; Zhao L; Baran CP; Nana-Sinkam PS; Wewers MD; Romberger D; Marsh CB; Parinandi NL
Cell Biochem Biophys 2013 Nov; 67(2):415-429
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.
Agriculture; Agricultural-industry; Agricultural-workers; Animal-husbandry-workers; Poultry; Poultry-industry; Poultry-workers; Organic-dusts; Airborne-dusts; Airborne-particles; Particulate-dust; Respiratory-system-disorders; Pulmonary-system-disorders; Lung-disorders; Lung-cells; Lipases; Cell-cultures; Immune-reaction; Cellular-reactions; Airway-obstruction; Dust-inhalation; Dust-particles;
Author Keywords: Phospholipase A2; IL-8; ERK; MAPK; Lung epithelial cell; Poultry dust; Agricultural PM; cPLA2 serine phosphorylation; Inflammatory cytokines; Interleukin-8; Respiratory epithelium; A549 cells
Narasimham L Parinandi, 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
Agriculture, Forestry and Fishing
Cell Biochemistry and Biophysics
University of Nebraska Medical Center, Omaha, Nebraska