Ozone-induced lung injury and sterile inflammation. Role of toll-like receptor 4

Agnieszka J. Connor, Jeffrey D. Laskin, Debra L. Laskin

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Inhalation of toxic doses of ozone is associated with a sterile inflammatory response characterized by an accumulation of macrophages in the lower lung which are activated to release cytotoxic/proinflammatory mediators that contribute to tissue injury. Toll-like receptor 4 (TLR4) is a pattern recognition receptor present on macrophages that has been implicated in sterile inflammatory responses. In the present studies we used TLR4 mutant C3H/HeJ mice to analyze the role of TLR4 in ozone-induced lung injury, oxidative stress and inflammation. Acute exposure of control C3H/HeOuJ mice to ozone (0.8. ppm for 3. h) resulted in increases in bronchoalveolar lavage (BAL) lipocalin 24p3 and 4-hydroxynonenal modified protein, markers of oxidative stress and lipid peroxidation. This was correlated with increases in BAL protein, as well as numbers of alveolar macrophages. Levels of surfactant protein-D, a pulmonary collectin known to regulate macrophage inflammatory responses, also increased in BAL following ozone inhalation. Ozone inhalation was associated with classical macrophage activation, as measured by increased NF-κB binding activity and expression of TNFα mRNA. The observation that these responses to ozone were not evident in TLR4 mutant C3H/HeJ mice demonstrates that functional TLR4 contributes to ozone-induced sterile inflammation and macrophage activation.

Original languageEnglish (US)
Pages (from-to)229-235
Number of pages7
JournalExperimental and Molecular Pathology
Volume92
Issue number2
DOIs
StatePublished - Apr 2012

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Clinical Biochemistry

Keywords

  • Macrophages
  • NF-κB
  • Ozone
  • Sterile inflammation
  • TLR4
  • TNFα

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