The effects of PM10 particles and oxidative stress on macrophages and lung epithelial cells: modulating effects of calcium-signaling antagonists.
We have previously examined the ability of air pollution particles (PM(10)) to promote release of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) 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-alpha production via calcium signaling in the mouse macrophage cell line (J774). The oxidant tBHP significantly increased intracellular calcium and the release of TNF-alpha 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 PM(10)-treated macrophages and epithelial cells by using conditioned medium (CM) from PM(10)-treated mononuclear cells to stimulate the release of the neutrophil chemoattractant chemokine IL-8 from A549 lung epithelial cells. TNF-alpha protein release was demonstrated in human mononuclear cells after PM(10) treatment, an effect that was inhibited by calcium antagonists. Treatment of A549 cells with monocyte/PM(10) CM produced increased IL-8 release that was reduced with CM from monocyte/PM(10)/calcium antagonist treatments. The expression of ICAM-1 was increased after incubation with CM from monocyte/PM(10) treatment, and this increase was prevented by treatment with CM from monocyte/PM(10)/calcium antagonist. These data demonstrate a link between oxidative stress, calcium, and inflammatory mediator production in macrophages and lung epithelial cells.
Brown
David M
DM
School of Life Sciences, Napier Univ., 10 Colinton Road, Edinburgh EH10 5DT, United Kingdom. da.brown@napier.ac.uk
Hutchison
Laura
L
Donaldson
Kenneth
K
Stone
Vicki
V
D000393:Air Pollutants / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000276:immunology*; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D000393:Air Pollutants; D002121:Calcium Channel Blockers; D017077:Culture Media, Conditioned; D016209:Interleukin-8; D016877:Oxidants; D018799:Intercellular Adhesion Molecule-1; D020122:tert-Butylhydroperoxide; D014700:Verapamil; D002118:Calcium