17β-Estradiol affects lung function and inflammation following ozone exposure in a sex-specific manner

Nathalie Fuentes, Marvin Nicoleau, Noe Cabello, Deborah Montes, Naseem Zomorodi, Zissis C. Chroneos, Patricia Silveyra

Research output: Contribution to journalArticle

Abstract

Inflammatory lung diseases affect men and women disproportionately, suggesting that fluctuations of circulating hormone levels mediate inflammatory responses. Studies have shown that ozone exposure contributes to lung injury and impairment of innate immunity with differential effects in men and women. Here, we hypothesized that 17β-estradiol enhances inflammation and airway hyperresponsiveness (AHR), triggered by ozone exposure, in the female lung. We performed gonadectomy and hormone treatment (17β-estradiol, 2 wk) in C57BL/6J female and male mice and exposed animals to 1 ppm of ozone or filtered air for 3 h. Twenty-four hours later, we tested lung function, inflammatory gene expression, and changes in bronchoalveolar lavage fluid (BALF). We found increased AHR and expression of inflammatory genes after ozone exposure. These changes were higher in females and were affected by gonadectomy and 17β-estradiol treatment in a sex-specific manner. Gonadectomized male mice displayed higher AHR and inflammatory gene expression than controls exposed to ozone; 17β-estradiol treatment did not affect this response. In females, ovariectomy reduced ozone-induced AHR, which was restored by 17β-estradiol treatment. Ozone exposure also increased BALF lipocalin-2, which was reduced in both male and female gonadectomized mice. Treatment with 17β-estradiol increased lipocalin-2 levels in females but lowered them in males. Gonadectomy also reduced ozone-induced expression of lung IL-6 and macrophage inflammatory protein-3 in females, which was restored by treatment with 17β-estradiol. Together, these results indicate that 17β-estradiol increases ozone-induced inflammation and AHR in females but not in males. Future studies examining diseases associated with air pollution exposure should consider the patient's sex and hormonal status.

Original languageEnglish (US)
Pages (from-to)L702-L716
JournalAmerican journal of physiology. Lung cellular and molecular physiology
Volume317
Issue number5
DOIs
StatePublished - Nov 1 2019

Fingerprint

Ozone
Estradiol
Pneumonia
Bronchoalveolar Lavage Fluid
Gene Expression
Lung
Therapeutics
Hormones
Inflammation
Macrophage Inflammatory Proteins
Air Pollution
Lung Injury
Ovariectomy
Innate Immunity
Lung Diseases
Interleukin-6
Air

All Science Journal Classification (ASJC) codes

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

Cite this

Fuentes, Nathalie ; Nicoleau, Marvin ; Cabello, Noe ; Montes, Deborah ; Zomorodi, Naseem ; Chroneos, Zissis C. ; Silveyra, Patricia. / 17β-Estradiol affects lung function and inflammation following ozone exposure in a sex-specific manner. In: American journal of physiology. Lung cellular and molecular physiology. 2019 ; Vol. 317, No. 5. pp. L702-L716.
@article{061af95fe8c947c4879322e866edd872,
title = "17β-Estradiol affects lung function and inflammation following ozone exposure in a sex-specific manner",
abstract = "Inflammatory lung diseases affect men and women disproportionately, suggesting that fluctuations of circulating hormone levels mediate inflammatory responses. Studies have shown that ozone exposure contributes to lung injury and impairment of innate immunity with differential effects in men and women. Here, we hypothesized that 17β-estradiol enhances inflammation and airway hyperresponsiveness (AHR), triggered by ozone exposure, in the female lung. We performed gonadectomy and hormone treatment (17β-estradiol, 2 wk) in C57BL/6J female and male mice and exposed animals to 1 ppm of ozone or filtered air for 3 h. Twenty-four hours later, we tested lung function, inflammatory gene expression, and changes in bronchoalveolar lavage fluid (BALF). We found increased AHR and expression of inflammatory genes after ozone exposure. These changes were higher in females and were affected by gonadectomy and 17β-estradiol treatment in a sex-specific manner. Gonadectomized male mice displayed higher AHR and inflammatory gene expression than controls exposed to ozone; 17β-estradiol treatment did not affect this response. In females, ovariectomy reduced ozone-induced AHR, which was restored by 17β-estradiol treatment. Ozone exposure also increased BALF lipocalin-2, which was reduced in both male and female gonadectomized mice. Treatment with 17β-estradiol increased lipocalin-2 levels in females but lowered them in males. Gonadectomy also reduced ozone-induced expression of lung IL-6 and macrophage inflammatory protein-3 in females, which was restored by treatment with 17β-estradiol. Together, these results indicate that 17β-estradiol increases ozone-induced inflammation and AHR in females but not in males. Future studies examining diseases associated with air pollution exposure should consider the patient's sex and hormonal status.",
author = "Nathalie Fuentes and Marvin Nicoleau and Noe Cabello and Deborah Montes and Naseem Zomorodi and Chroneos, {Zissis C.} and Patricia Silveyra",
year = "2019",
month = "11",
day = "1",
doi = "10.1152/ajplung.00176.2019",
language = "English (US)",
volume = "317",
pages = "L702--L716",
journal = "American Journal of Physiology",
issn = "1040-0605",
publisher = "American Physiological Society",
number = "5",

}

17β-Estradiol affects lung function and inflammation following ozone exposure in a sex-specific manner. / Fuentes, Nathalie; Nicoleau, Marvin; Cabello, Noe; Montes, Deborah; Zomorodi, Naseem; Chroneos, Zissis C.; Silveyra, Patricia.

In: American journal of physiology. Lung cellular and molecular physiology, Vol. 317, No. 5, 01.11.2019, p. L702-L716.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 17β-Estradiol affects lung function and inflammation following ozone exposure in a sex-specific manner

AU - Fuentes, Nathalie

AU - Nicoleau, Marvin

AU - Cabello, Noe

AU - Montes, Deborah

AU - Zomorodi, Naseem

AU - Chroneos, Zissis C.

AU - Silveyra, Patricia

PY - 2019/11/1

Y1 - 2019/11/1

N2 - Inflammatory lung diseases affect men and women disproportionately, suggesting that fluctuations of circulating hormone levels mediate inflammatory responses. Studies have shown that ozone exposure contributes to lung injury and impairment of innate immunity with differential effects in men and women. Here, we hypothesized that 17β-estradiol enhances inflammation and airway hyperresponsiveness (AHR), triggered by ozone exposure, in the female lung. We performed gonadectomy and hormone treatment (17β-estradiol, 2 wk) in C57BL/6J female and male mice and exposed animals to 1 ppm of ozone or filtered air for 3 h. Twenty-four hours later, we tested lung function, inflammatory gene expression, and changes in bronchoalveolar lavage fluid (BALF). We found increased AHR and expression of inflammatory genes after ozone exposure. These changes were higher in females and were affected by gonadectomy and 17β-estradiol treatment in a sex-specific manner. Gonadectomized male mice displayed higher AHR and inflammatory gene expression than controls exposed to ozone; 17β-estradiol treatment did not affect this response. In females, ovariectomy reduced ozone-induced AHR, which was restored by 17β-estradiol treatment. Ozone exposure also increased BALF lipocalin-2, which was reduced in both male and female gonadectomized mice. Treatment with 17β-estradiol increased lipocalin-2 levels in females but lowered them in males. Gonadectomy also reduced ozone-induced expression of lung IL-6 and macrophage inflammatory protein-3 in females, which was restored by treatment with 17β-estradiol. Together, these results indicate that 17β-estradiol increases ozone-induced inflammation and AHR in females but not in males. Future studies examining diseases associated with air pollution exposure should consider the patient's sex and hormonal status.

AB - Inflammatory lung diseases affect men and women disproportionately, suggesting that fluctuations of circulating hormone levels mediate inflammatory responses. Studies have shown that ozone exposure contributes to lung injury and impairment of innate immunity with differential effects in men and women. Here, we hypothesized that 17β-estradiol enhances inflammation and airway hyperresponsiveness (AHR), triggered by ozone exposure, in the female lung. We performed gonadectomy and hormone treatment (17β-estradiol, 2 wk) in C57BL/6J female and male mice and exposed animals to 1 ppm of ozone or filtered air for 3 h. Twenty-four hours later, we tested lung function, inflammatory gene expression, and changes in bronchoalveolar lavage fluid (BALF). We found increased AHR and expression of inflammatory genes after ozone exposure. These changes were higher in females and were affected by gonadectomy and 17β-estradiol treatment in a sex-specific manner. Gonadectomized male mice displayed higher AHR and inflammatory gene expression than controls exposed to ozone; 17β-estradiol treatment did not affect this response. In females, ovariectomy reduced ozone-induced AHR, which was restored by 17β-estradiol treatment. Ozone exposure also increased BALF lipocalin-2, which was reduced in both male and female gonadectomized mice. Treatment with 17β-estradiol increased lipocalin-2 levels in females but lowered them in males. Gonadectomy also reduced ozone-induced expression of lung IL-6 and macrophage inflammatory protein-3 in females, which was restored by treatment with 17β-estradiol. Together, these results indicate that 17β-estradiol increases ozone-induced inflammation and AHR in females but not in males. Future studies examining diseases associated with air pollution exposure should consider the patient's sex and hormonal status.

UR - http://www.scopus.com/inward/record.url?scp=85074551724&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85074551724&partnerID=8YFLogxK

U2 - 10.1152/ajplung.00176.2019

DO - 10.1152/ajplung.00176.2019

M3 - Article

C2 - 31553636

AN - SCOPUS:85074551724

VL - 317

SP - L702-L716

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 1040-0605

IS - 5

ER -