The effects of PM10 particles and oxidative stress on macrophages and lung epithelial cells: Modulating effects of calcium-signaling antagonists

David M. Brown, Laura Hutchison, Kenneth Donaldson, Vicki Stone

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

Abstract

We have previously examined the ability of air pollution particles (PM 10) to promote release of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) 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-α production via calcium signaling in the mouse macrophage cell line (J774). The oxidant tBHP significantly increased intracellular calcium and the release of TNF-α 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-α 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.

Original languageEnglish
Pages (from-to)L1444-L1451
Number of pages8
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume292
Issue number6
DOIs
Publication statusPublished - Jun 2007

Keywords

  • Cytokines
  • Lung macrophages

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Fingerprint

Dive into the research topics of 'The effects of PM10 particles and oxidative stress on macrophages and lung epithelial cells: Modulating effects of calcium-signaling antagonists'. Together they form a unique fingerprint.

Cite this