Sex Differences in Pulmonary Eicosanoids and Specialized Pro-Resolving Mediators in Response to Ozone Exposure.
air pollution
inflammation
lipids
lung
sex differences
Journal
Toxicological sciences : an official journal of the Society of Toxicology
ISSN: 1096-0929
Titre abrégé: Toxicol Sci
Pays: United States
ID NLM: 9805461
Informations de publication
Date de publication:
30 08 2021
30 08 2021
Historique:
pubmed:
28
6
2021
medline:
30
9
2021
entrez:
27
6
2021
Statut:
ppublish
Résumé
Ozone (O3) is a criteria air pollutant known to increase the morbidity and mortality of cardiopulmonary diseases. This occurs through a pulmonary inflammatory response characterized by increased recruitment of immune cells into the airspace, pro-inflammatory cytokines, and pro-inflammatory lipid mediators. Recent evidence has demonstrated sex-dependent differences in the O3-induced pulmonary inflammatory response. However, it is unknown if this dimorphic response is evident in pulmonary lipid mediator metabolism. We hypothesized that there are sex-dependent differences in lipid mediator production following acute O3 exposure. Male and female C57BL/6J mice were exposed to 1 part per million O3 for 3 h and were necropsied at 6 or 24 h following exposure. Lung lavage was collected for cell differential and total protein analysis, and lung tissue was collected for mRNA analysis, metabololipidomics, and immunohistochemistry. Compared with males, O3-exposed female mice had increases in airspace neutrophilia, neutrophil chemokine mRNA, pro-inflammatory eicosanoids such as prostaglandin E2, and specialized pro-resolving mediators (SPMs), such as resolvin D5 in lung tissue. Likewise, precursor fatty acids (arachidonic and docosahexaenoic acid; DHA) were increased in female lung tissue following O3 exposure compared with males. Experiments with ovariectomized females revealed that loss of ovarian hormones exacerbates pulmonary inflammation and injury. However, eicosanoid and SPM production were not altered by ovariectomy despite depleted pulmonary DHA concentrations. Taken together, these data indicate that O3 drives an increased pulmonary inflammatory and bioactive lipid mediator response in females. Furthermore, ovariectomy increases susceptibility to O3-induced pulmonary inflammation and injury, as well as decreases pulmonary DHA concentrations.
Identifiants
pubmed: 34175951
pii: 6310193
doi: 10.1093/toxsci/kfab081
pmc: PMC8404991
doi:
Substances chimiques
Eicosanoids
0
Ozone
66H7ZZK23N
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
170-183Subventions
Organisme : NIEHS NIH HHS
ID : P30 ES025128
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR025780
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES020897
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES031378
Pays : United States
Organisme : NIEHS NIH HHS
ID : T32 ES007046
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES027574
Pays : United States
Organisme : NIH HHS
ID : S10 OD010366
Pays : United States
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of the Society of Toxicology.All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.