Modulatory effects of ozone on THP-1 cells in response to SP-A stimulation

Branislava Janic, Todd M. Umstead, David S. Phelps, Joanna Floros

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Ozone (O3), a major component of air polludon and a strong oxidizing agent, can lead to lung injury associated with edema, inflammation, and epithelial cell damage. The effects of O3 on pulmonary immune cells have been studied in various in vivo and in vitro systems. We have shown previously that O3 exposure of surfactant protein (SP)-A decreases its ability to modulate proinflammatory cytokine production by cells of monocyte/macrophage lineage (THP-1 cells). In this report, we exposed THP-1 cells and/or native SP-A obtained from bronchoalveolar lavage of patients with alveolar proteinosis to O3 and studied cytokine production and NF-κB signaling. The results showed 1) exposure of THP-1 cells to O 3 significantly decreased their ability to express TNF-α in response to SP-A; TNF-α production, under these conditions, was still significantly higher than basal (unstimulated) levels in filtered air-exposed THP-1 cells; 2) exposure of both THP-1 cells and SP-A to O3 did not result in any significant differences in TNF-α expression compared with basal levels; 3) O3 exposure of SP-A resulted in a decreased ability of SP-A to activate the NF-κB pathway, as assessed by the lack of significant increase and decrease of the nuclear p65 subunit of NF-κB and cytoplasmic IκBα, respectively; and 4) O3 exposure of THP-1 cells resulted in a decrease in SP-A-mediated THP-1 cell responsiveness, which did not seem to be mediated via the classic NF-κB pathway. These findings indicate that O3 exposure may mediate its effect on macrophage function both directly and indirectly (via SP-A oxidation) and by involving different mechanisms.

Original languageEnglish (US)
Pages (from-to)L317-L325
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume288
Issue number2 32-2
DOIs
StatePublished - Feb 2005

All Science Journal Classification (ASJC) codes

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

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