Sex differences in the expression of lung inflammatory mediators in response to ozone

Noe Cabello, Vikas Mishra, Utkarshna Sinha, Susan L. Diangelo, Zissis C. Chroneos, Ndifreke A. Ekpa, Timothy K. Cooper, Carla R. Caruso, Patricia Silveyra

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Sex differences in the incidence of respiratory diseases have been reported. Women are more susceptible to inflammatory lung disease induced by air pollution and show worse adverse pulmonary health outcomes than men. However, the mechanisms underlying these differences remain unknown. In the present study, we hypothesized that sex differences in the expression of lung inflammatory mediators affect sex-specific immune responses to environmental toxicants. We focused on the effects of ground-level ozone, a major air pollutant, in the expression and regulation of lung immunity genes. We exposed adult male and female mice to 2 ppm of ozone or filtered air (control) for 3 h. We compared mRNA levels of 84 inflammatory genes in lungs harvested 4 h postexposure using a PCR array. We also evaluated changes in lung histology and bronchoalveolar lavage fluid cell counts and protein content at 24 and 72 h postexposure. Our results revealed sex differences in lung inflammation triggered by ozone exposure and in the expression of genes involved in acute phase and inflammatory responses. Major sex differences were found in the expression of neutrophil-attracting chemokines (Ccl20, Cxcl5, and Cxcl2), the proinflammatory cytokine interleukin-6, and oxidative stress-related enzymes (Ptgs2, Nos2). In addition, the phosphorylation of STAT3, known to mediate IL-6-related immune responses, was significantly higher in ozone-exposed mice. Together, our observations suggest that a differential regulation of the lung immune response could be implicated in the observed increased susceptibility to adverse health effects from ozone observed in women vs. men.

Original languageEnglish (US)
Pages (from-to)L1150-L1163
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume309
Issue number10
DOIs
StatePublished - Jan 1 2015

Fingerprint

Ozone
Sex Characteristics
Lung
Bronchoalveolar Lavage Fluid
Interleukin-6
Men's Health
Air Pollutants
Acute-Phase Reaction
Air Pollution
Chemokines
Lung Diseases
Genes
Immunity
Pneumonia
Histology
Oxidative Stress
Neutrophils
Cell Count
Air
Phosphorylation

All Science Journal Classification (ASJC) codes

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

Cite this

Cabello, Noe ; Mishra, Vikas ; Sinha, Utkarshna ; Diangelo, Susan L. ; Chroneos, Zissis C. ; Ekpa, Ndifreke A. ; Cooper, Timothy K. ; Caruso, Carla R. ; Silveyra, Patricia. / Sex differences in the expression of lung inflammatory mediators in response to ozone. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2015 ; Vol. 309, No. 10. pp. L1150-L1163.
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Sex differences in the expression of lung inflammatory mediators in response to ozone. / Cabello, Noe; Mishra, Vikas; Sinha, Utkarshna; Diangelo, Susan L.; Chroneos, Zissis C.; Ekpa, Ndifreke A.; Cooper, Timothy K.; Caruso, Carla R.; Silveyra, Patricia.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 309, No. 10, 01.01.2015, p. L1150-L1163.

Research output: Contribution to journalArticle

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AU - Cabello, Noe

AU - Mishra, Vikas

AU - Sinha, Utkarshna

AU - Diangelo, Susan L.

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AU - Ekpa, Ndifreke A.

AU - Cooper, Timothy K.

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AU - Silveyra, Patricia

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AB - Sex differences in the incidence of respiratory diseases have been reported. Women are more susceptible to inflammatory lung disease induced by air pollution and show worse adverse pulmonary health outcomes than men. However, the mechanisms underlying these differences remain unknown. In the present study, we hypothesized that sex differences in the expression of lung inflammatory mediators affect sex-specific immune responses to environmental toxicants. We focused on the effects of ground-level ozone, a major air pollutant, in the expression and regulation of lung immunity genes. We exposed adult male and female mice to 2 ppm of ozone or filtered air (control) for 3 h. We compared mRNA levels of 84 inflammatory genes in lungs harvested 4 h postexposure using a PCR array. We also evaluated changes in lung histology and bronchoalveolar lavage fluid cell counts and protein content at 24 and 72 h postexposure. Our results revealed sex differences in lung inflammation triggered by ozone exposure and in the expression of genes involved in acute phase and inflammatory responses. Major sex differences were found in the expression of neutrophil-attracting chemokines (Ccl20, Cxcl5, and Cxcl2), the proinflammatory cytokine interleukin-6, and oxidative stress-related enzymes (Ptgs2, Nos2). In addition, the phosphorylation of STAT3, known to mediate IL-6-related immune responses, was significantly higher in ozone-exposed mice. Together, our observations suggest that a differential regulation of the lung immune response could be implicated in the observed increased susceptibility to adverse health effects from ozone observed in women vs. men.

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