Airborne agricultural particulate matter induces inflammatory cytokine secretion by respiratory epithelial cells: Mechanisms of regulation by eicosanoid lipid signal mediators

摘要

The purpose of this study was to elucidate the mechanism of the airborne poultry dust (particulate matter, PM)-inducedrespiratory tract inflammation, a common symptom in agricultural respiratory diseases. The study was based on thehypothesis that poultry PM would induce the release of inflammatory cytokine interleukin-8 (IL-8) by respiratory epithelialcells under the upstream regulation by cytosolic phospholipase A2 (cPLA2) activation and subsequent formation ofcyclooxygenase (COX)- and lipoxygenase (LOX)-catalyzed arachidonic acid (AA) metabolites (eicosanoids). Human lungepithelial cells (A549) in culture were treated with the poultry PM (0.1-1.0 mg) for different lengths of time, followingwhich PLA2 activity, release of eicosanoids and secretion of IL-8 in cells were determined. Poultry PM (1.0 mg/ml) causeda significant activation of PLA2 in a time-dependent manner (15-60 min), which was significantly attenuated by thecalcium-chelating agents, cPLA2-specific inhibitor (AACOCF3) and antioxidant (vitamin C) in A549 cells. Poultry PMalso significantly induced the release of COX- and LOX-catalyzed eicosanoids (prostaglandins, thromboxane A2 andleukotrienes B4 and C4) and upstream activation of AA LOX in the cells. Poultry PM also significantly induced releaseof IL-8 by the cells in a dose- and time-dependent manner, which was significantly attenuated by the calcium chelatingagents, antioxidants and COX- and LOX-specific inhibitors. The current study for the first time revealed that thepoultry 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.