Airborne agricultural particulate matter induces inflammatory cytokine secretion by respiratory epithelial cells: mechanisms of regulation by eicosanoid lipid signal mediators.
The purpose of this study was to elucidate the mechanism of the airborne poultry dust (particulate matter, PM)-induced respiratory tract inflammation, a common symptom in agricultural respiratory diseases. The study was based on the hypothesis that poultry PM would induce the release of inflammatory cytokine interleukin-8 (IL-8) by respiratory epithelial cells under the upstream regulation by cytosolic phospholipase A2 (cPLA2) activation and subsequent formation of cyclooxygenase (COX)- and lipoxygenase (LOX)-catalyzed arachidonic acid (AA) metabolites (eicosanoids). Human lung epithelial cells (A549) in culture were treated with the poultry PM (0.1-1.0 mg) for different lengths of time, following which PLA2 activity, release of eicosanoids and secretion of IL-8 in cells were determined. Poultry PM (1.0 mg/ml) caused a significant activation of PLA2 in a time-dependent manner (15-60 min), which was significantly attenuated by the calcium-chelating agents, cPLA2-specific inhibitor (AACOCF3) and antioxidant (vitamin C) in A549 cells. Poultry PM also significantly induced the release of COX- and LOX-catalyzed eicosanoids (prostaglandins, thromboxane A2 and leukotrienes B4 and C4) and upstream activation of AA LOX in the cells. Poultry PM also significantly induced release of IL-8 by the cells in a dose- and time-dependent manner, which was significantly attenuated by the calcium chelating agents, antioxidants and COX- and LOX-specific inhibitors. The current study for the first time revealed that the poultry PM-induced IL-8 release from the respiratory epithelial cells was regulated upstream by reactive oxygen species, cPLA2-, COX- and LOX-derived eicosanoid lipid signal mediators.
Smitha
S
Malireddy
Courtney
C
Lawson
Emily
E
Steinhour
Judy
J
Hart
Sainath R
SR
Kotha
Rishi B
RB
Patel
Lingying
L
Zhao
John R
JR
Wilkins
Clay B
CB
Marsh
Ulysses J
UJ
Magalang
Debra
D
Romberger
Mark D
MD
Wewers
Narasimham L
NL
Parinandi
D000383:Agriculture; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D055162:Biocatalysis; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D015777:Eicosanoids / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D058945:Lipoxygenases / Q000378:metabolism; D052638:Particulate Matter / Q000737:chemistry / Q000494:pharmacology*; D054510:Phospholipases A2, Cytosolic / Q000037:antagonists & inhibitors / Q000378:metabolism; D011200:Poultry; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D012997:Solvents / Q000737:chemistry; D013997:Time Factors
D000975:Antioxidants; D016207:Cytokines; D015777:Eicosanoids; D004791:Enzyme Inhibitors; D016209:Interleukin-8; D052638:Particulate Matter; D017382:Reactive Oxygen Species; D012997:Solvents; D016718:Arachidonic Acid; D004533:Egtazic Acid; D058945:Lipoxygenases; D011451:Prostaglandin-Endoperoxide Synthases; D054510:Phospholipases A2, Cytosolic; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid