Modulation by Ozone of Glucocorticoid-Regulating Factors in the Lungs in Relation to Stress Axis Reactivity

Exposure to air pollutants increases levels of circulating glucocorticoid stress hormones that exert profound effects relevant to health and disease. However, the nature and magnitude of tissue-level effects are modulated by factors that regulate local glucocorticoid activity; accordingly, inter-ind...

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Autores principales:	Jith Thomas, Errol M. Thomson
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	ozone glucocorticoid glucocorticoid metabolism corticosteroid-binding globulin elastase inflammation Chemical technology TP1-1185
Acceso en línea:	https://doaj.org/article/f80e1a05802842a6905606b806320a7b
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spelling	oai:doaj.org-article:f80e1a05802842a6905606b806320a7b2021-11-25T19:08:08ZModulation by Ozone of Glucocorticoid-Regulating Factors in the Lungs in Relation to Stress Axis Reactivity10.3390/toxics91102902305-6304https://doaj.org/article/f80e1a05802842a6905606b806320a7b2021-11-01T00:00:00Zhttps://www.mdpi.com/2305-6304/9/11/290https://doaj.org/toc/2305-6304Exposure to air pollutants increases levels of circulating glucocorticoid stress hormones that exert profound effects relevant to health and disease. However, the nature and magnitude of tissue-level effects are modulated by factors that regulate local glucocorticoid activity; accordingly, inter-individual differences could contribute to susceptibility. In the present study, we characterized effects of ozone (O<sub>3</sub>) inhalation on glucocorticoid-regulating factors in the lungs of rat strains with contrasting hypothalamic–pituitary–adrenal stress axis responses. Hyper-responsive Fischer (F344) and less responsive Lewis (LEW) rats were exposed to air or 0.8 ppm O<sub>3</sub> for 4 h by nose-only inhalation. Levels of the high-specificity and -affinity corticosteroid-binding globulin protein increased in the lungs of both strains proportional to the rise in corticosterone levels following O<sub>3</sub> exposure. Ozone reduced the ratio of 11β-hydroxysteroid dehydrogenase type 1 (HSDB1)/HSDB2 mRNA in the lungs of F344 but not LEW, indicating strain-specific transcriptional regulation of the major glucocorticoid metabolism factors that control tissue-level action. Intercellular adhesion molecule (ICAM)-1 and total elastase activity were increased by O<sub>3</sub> in both strains, consistent with extravasation and tissue remodeling processes following injury. However, mRNA levels of inflammatory markers were significantly higher in the lungs of O<sub>3</sub>-exposed LEW compared to F344. The data show that strain differences in the glucocorticoid response to O<sub>3</sub> are accompanied by corresponding changes in regulatory factors, and that these effects are collectively associated with a differential inflammatory response to O<sub>3</sub>. Innate differences in glucocorticoid regulatory factors may modulate the pulmonary effects of inhaled pollutants, thereby contributing to differential susceptibility.Jith ThomasErrol M. ThomsonMDPI AGarticleozoneglucocorticoidglucocorticoid metabolismcorticosteroid-binding globulinelastaseinflammationChemical technologyTP1-1185ENToxics, Vol 9, Iss 290, p 290 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ozone glucocorticoid glucocorticoid metabolism corticosteroid-binding globulin elastase inflammation Chemical technology TP1-1185
spellingShingle	ozone glucocorticoid glucocorticoid metabolism corticosteroid-binding globulin elastase inflammation Chemical technology TP1-1185 Jith Thomas Errol M. Thomson Modulation by Ozone of Glucocorticoid-Regulating Factors in the Lungs in Relation to Stress Axis Reactivity
description	Exposure to air pollutants increases levels of circulating glucocorticoid stress hormones that exert profound effects relevant to health and disease. However, the nature and magnitude of tissue-level effects are modulated by factors that regulate local glucocorticoid activity; accordingly, inter-individual differences could contribute to susceptibility. In the present study, we characterized effects of ozone (O<sub>3</sub>) inhalation on glucocorticoid-regulating factors in the lungs of rat strains with contrasting hypothalamic–pituitary–adrenal stress axis responses. Hyper-responsive Fischer (F344) and less responsive Lewis (LEW) rats were exposed to air or 0.8 ppm O<sub>3</sub> for 4 h by nose-only inhalation. Levels of the high-specificity and -affinity corticosteroid-binding globulin protein increased in the lungs of both strains proportional to the rise in corticosterone levels following O<sub>3</sub> exposure. Ozone reduced the ratio of 11β-hydroxysteroid dehydrogenase type 1 (HSDB1)/HSDB2 mRNA in the lungs of F344 but not LEW, indicating strain-specific transcriptional regulation of the major glucocorticoid metabolism factors that control tissue-level action. Intercellular adhesion molecule (ICAM)-1 and total elastase activity were increased by O<sub>3</sub> in both strains, consistent with extravasation and tissue remodeling processes following injury. However, mRNA levels of inflammatory markers were significantly higher in the lungs of O<sub>3</sub>-exposed LEW compared to F344. The data show that strain differences in the glucocorticoid response to O<sub>3</sub> are accompanied by corresponding changes in regulatory factors, and that these effects are collectively associated with a differential inflammatory response to O<sub>3</sub>. Innate differences in glucocorticoid regulatory factors may modulate the pulmonary effects of inhaled pollutants, thereby contributing to differential susceptibility.
format	article
author	Jith Thomas Errol M. Thomson
author_facet	Jith Thomas Errol M. Thomson
author_sort	Jith Thomas
title	Modulation by Ozone of Glucocorticoid-Regulating Factors in the Lungs in Relation to Stress Axis Reactivity
title_short	Modulation by Ozone of Glucocorticoid-Regulating Factors in the Lungs in Relation to Stress Axis Reactivity
title_full	Modulation by Ozone of Glucocorticoid-Regulating Factors in the Lungs in Relation to Stress Axis Reactivity
title_fullStr	Modulation by Ozone of Glucocorticoid-Regulating Factors in the Lungs in Relation to Stress Axis Reactivity
title_full_unstemmed	Modulation by Ozone of Glucocorticoid-Regulating Factors in the Lungs in Relation to Stress Axis Reactivity
title_sort	modulation by ozone of glucocorticoid-regulating factors in the lungs in relation to stress axis reactivity
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f80e1a05802842a6905606b806320a7b
work_keys_str_mv	AT jiththomas modulationbyozoneofglucocorticoidregulatingfactorsinthelungsinrelationtostressaxisreactivity AT errolmthomson modulationbyozoneofglucocorticoidregulatingfactorsinthelungsinrelationtostressaxisreactivity
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Modulation by Ozone of Glucocorticoid-Regulating Factors in the Lungs in Relation to Stress Axis Reactivity

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