Increased nitric oxide synthase in the lung after ozone inhalation is associated with activation of NF-κB

Debra L. Laskin, Vasanthi Sunil, Yan Guo, Diane E. Heck, Jeffrey D. Laskin

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Acute inhalation of ozone is associated with an inflammatory response characterized by the accumulation of macrophages at sites of tissue injury. These cells, along with resident alveolar epithelial cells, become activated and release cytotoxic and proinflammatory mediators, such as nitric oxide (̇NO), that we speculate contribute to toxicity. In these studies we analyzed mechanisms regulating increased ̇NO synthase activity in lung macrophages and type II cells after ozone inhalation. Brief exposure of rats to ozone (2 ppm for 3 hr) resulted in an increase in ̇NO production by alveolar macrophages as well as type II cells in response to the inflammatory mediators lipopolysaccharide and interferon γ. These effects were apparently due to increased expression of inducible ̇NO synthase (iNOS) protein and mRNA, which were evident in vitro and in situ in histologic sections. ̇NO production and iNOS protein expression by both macrophages and epithelial cells were blocked by pyrrolidine dithiocarbamate (PDTC), an agent that inhibits activity of nuclear transcription factor kappa B (NF-κB). Cells from ozone-treated animals were less sensitive to the effects of PDTC than cells from control animals. Using electrophoretic mobility shift assays, we measured NF-κB binding activity in nuclear extracts of cells from control and ozone-exposed animals. Treatment of rats with ozone resulted in a time-dependent increase in NF-κB binding activity in both cell types, reaching a maximum in cells isolated 12 to 24 hr after ozone inhalation. Taken together, these data suggest that changes in the activity of NF-κB signaling are important in the response of lung macrophages and type II epithelial cells to cytokines after ozone inhalation.

Original languageEnglish (US)
Pages (from-to)1175-1178
Number of pages4
JournalEnvironmental health perspectives
Volume106
Issue numberSUPPL. 5
DOIs
StatePublished - 1998

All Science Journal Classification (ASJC) codes

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

Keywords

  • Alveolar macrophages
  • Interleukin-1
  • NF-κB
  • Nitric oxide
  • Ozone
  • Tumor necrosis factor
  • Type II cells

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