title: Phospholipase A(2) activation by poultry particulate matter is mediated through extracellular signal-regulated kinase in lung epithelial cells: regulation of interleukin-8 release.
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.
authors.affiliation: 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.
authors.forename: Sainath R
authors.initials: SR
authors.lastname: Kotha
authors.forename: Melissa G
authors.initials: MG
authors.lastname: Piper
authors.forename: Rishi B
authors.initials: RB
authors.lastname: Patel
authors.forename: Sean
authors.initials: S
authors.lastname: Sliman
authors.forename: Smitha
authors.initials: S
authors.lastname: Malireddy
authors.forename: Lingying
authors.initials: L
authors.lastname: Zhao
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Baran
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Nana-Sinkam
authors.forename: Mark D
authors.initials: MD
authors.lastname: Wewers
authors.forename: Debra
authors.initials: D
authors.lastname: Romberger
authors.forename: Clay B
authors.initials: CB
authors.lastname: Marsh
authors.forename: Narasimham L
authors.initials: NL
authors.lastname: Parinandi
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001798:Blood Proteins / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008168:Lung / Q000166:cytology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D052638:Particulate Matter / Q000494:pharmacology*; D054467:Phospholipases A2 / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011200:Poultry; D021381:Protein Transport / Q000187:drug effects; D012694:Serine / Q000378:metabolism; D013997:Time Factors
chemical_list: D001798:Blood Proteins; D016209:Interleukin-8; C400481:PLIalpha; D052638:Particulate Matter; D016718:Arachidonic Acid; D012694:Serine; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D054467:Phospholipases A2