Brown, David M, Hutchison, Laura, Donaldson, Ken and Stone, Vicki (2007) The effects of PM10 particles and oxidative stress on macrophages and lung epithelial cells: modulating effects of calcium-signaling antagonists. American Journal of Physiology. Lung Cellular and Molecular Physiology, 292 (6). L1444-L1451. ISSN 1522-1504

Abstract/Description

We have previously examined the ability of air pollution particles (PM10) to promote release of the proinflammatory cytokine tumor necrosis factor- (TNF-) from human peripheral blood mononuclear cells and demonstrated a role for calcium as a signaling molecule in this process. We have now studied the ability of oxidative stress induced by a synthetic oxidant tert-butyl hydroperoxide (tBHP) to induce TNF- production via calcium signaling in the mouse macrophage cell line (J774). The oxidant tBHP significantly increased intracellular calcium and the release of TNF- in J774 cells, an effect that was reduced to control levels by inhibition of calcium signaling with verapamil, BAPTA-AM, and W-7. This study also investigated interactions between PM10-treated macrophages and epithelial cells by using conditioned medium (CM) from PM10-treated mononuclear cells to stimulate the release of the neutrophil chemoattractant chemokine IL-8 from A549 lung epithelial cells. TNF- protein release was demonstrated in human mononuclear cells after PM10 treatment, an effect that was inhibited by calcium antagonists. Treatment of A549 cells with monocyte/PM10 CM produced increased IL-8 release that was reduced with CM from monocyte/PM10/calcium antagonist treatments. The expression of ICAM-1 was increased after incubation with CM from monocyte/PM10 treatment, and this increase was prevented by treatment with CM from monocyte/PM10/calcium antagonist. These data demonstrate a link between oxidative stress, calcium, and inflammatory mediator production in macrophages and lung epithelial cells.

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