Early life ozone exposure results in dysregulated innate immune function and altered microRNA expression in airway epithelium.

Exposure to ozone has been associated with increased incidence of respiratory morbidity in humans; however the mechanism(s) behind the enhancement of susceptibility are unclear. We have previously reported that exposure to episodic ozone during postnatal development results in an attenuated peripher...

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Autores principales:	Candice C Clay, Kinjal Maniar-Hew, Joan E Gerriets, Theodore T Wang, Edward M Postlethwait, Michael J Evans, Justin H Fontaine, Lisa A Miller
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/af9bf708e72d4cc38bc8b68447dab84b
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spelling	oai:doaj.org-article:af9bf708e72d4cc38bc8b68447dab84b2021-11-18T08:29:54ZEarly life ozone exposure results in dysregulated innate immune function and altered microRNA expression in airway epithelium.1932-620310.1371/journal.pone.0090401https://doaj.org/article/af9bf708e72d4cc38bc8b68447dab84b2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24594710/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Exposure to ozone has been associated with increased incidence of respiratory morbidity in humans; however the mechanism(s) behind the enhancement of susceptibility are unclear. We have previously reported that exposure to episodic ozone during postnatal development results in an attenuated peripheral blood cytokine response to lipopolysaccharide (LPS) that persists with maturity. As the lung is closely interfaced with the external environment, we hypothesized that the conducting airway epithelium of neonates may also be a target of immunomodulation by ozone. To test this hypothesis, we evaluated primary airway epithelial cell cultures derived from juvenile rhesus macaque monkeys with a prior history of episodic postnatal ozone exposure. Innate immune function was measured by expression of the proinflammatory cytokines IL-6 and IL-8 in primary cultures established following in vivo LPS challenge or, in response to in vitro LPS treatment. Postnatal ozone exposure resulted in significantly attenuated IL-6 mRNA and protein expression in primary cultures from juvenile animals; IL-8 mRNA was also significantly reduced. The effect of antecedent ozone exposure was modulated by in vivo LPS challenge, as primary cultures exhibited enhanced cytokine expression upon secondary in vitro LPS treatment. Assessment of potential IL-6-targeting microRNAs miR-149, miR-202, and miR-410 showed differential expression in primary cultures based upon animal exposure history. Functional assays revealed that miR-149 is capable of binding to the IL-6 3' UTR and decreasing IL-6 protein synthesis in airway epithelial cell lines. Cumulatively, our findings suggest that episodic ozone during early life contributes to the molecular programming of airway epithelium, such that memory from prior exposures is retained in the form of a dysregulated IL-6 and IL-8 response to LPS; differentially expressed microRNAs such as miR-149 may play a role in the persistent modulation of the epithelial innate immune response towards microbes in the mature lung.Candice C ClayKinjal Maniar-HewJoan E GerrietsTheodore T WangEdward M PostlethwaitMichael J EvansJustin H FontaineLisa A MillerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 3, p e90401 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Candice C Clay Kinjal Maniar-Hew Joan E Gerriets Theodore T Wang Edward M Postlethwait Michael J Evans Justin H Fontaine Lisa A Miller Early life ozone exposure results in dysregulated innate immune function and altered microRNA expression in airway epithelium.
description	Exposure to ozone has been associated with increased incidence of respiratory morbidity in humans; however the mechanism(s) behind the enhancement of susceptibility are unclear. We have previously reported that exposure to episodic ozone during postnatal development results in an attenuated peripheral blood cytokine response to lipopolysaccharide (LPS) that persists with maturity. As the lung is closely interfaced with the external environment, we hypothesized that the conducting airway epithelium of neonates may also be a target of immunomodulation by ozone. To test this hypothesis, we evaluated primary airway epithelial cell cultures derived from juvenile rhesus macaque monkeys with a prior history of episodic postnatal ozone exposure. Innate immune function was measured by expression of the proinflammatory cytokines IL-6 and IL-8 in primary cultures established following in vivo LPS challenge or, in response to in vitro LPS treatment. Postnatal ozone exposure resulted in significantly attenuated IL-6 mRNA and protein expression in primary cultures from juvenile animals; IL-8 mRNA was also significantly reduced. The effect of antecedent ozone exposure was modulated by in vivo LPS challenge, as primary cultures exhibited enhanced cytokine expression upon secondary in vitro LPS treatment. Assessment of potential IL-6-targeting microRNAs miR-149, miR-202, and miR-410 showed differential expression in primary cultures based upon animal exposure history. Functional assays revealed that miR-149 is capable of binding to the IL-6 3' UTR and decreasing IL-6 protein synthesis in airway epithelial cell lines. Cumulatively, our findings suggest that episodic ozone during early life contributes to the molecular programming of airway epithelium, such that memory from prior exposures is retained in the form of a dysregulated IL-6 and IL-8 response to LPS; differentially expressed microRNAs such as miR-149 may play a role in the persistent modulation of the epithelial innate immune response towards microbes in the mature lung.
format	article
author	Candice C Clay Kinjal Maniar-Hew Joan E Gerriets Theodore T Wang Edward M Postlethwait Michael J Evans Justin H Fontaine Lisa A Miller
author_facet	Candice C Clay Kinjal Maniar-Hew Joan E Gerriets Theodore T Wang Edward M Postlethwait Michael J Evans Justin H Fontaine Lisa A Miller
author_sort	Candice C Clay
title	Early life ozone exposure results in dysregulated innate immune function and altered microRNA expression in airway epithelium.
title_short	Early life ozone exposure results in dysregulated innate immune function and altered microRNA expression in airway epithelium.
title_full	Early life ozone exposure results in dysregulated innate immune function and altered microRNA expression in airway epithelium.
title_fullStr	Early life ozone exposure results in dysregulated innate immune function and altered microRNA expression in airway epithelium.
title_full_unstemmed	Early life ozone exposure results in dysregulated innate immune function and altered microRNA expression in airway epithelium.
title_sort	early life ozone exposure results in dysregulated innate immune function and altered microrna expression in airway epithelium.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/af9bf708e72d4cc38bc8b68447dab84b
work_keys_str_mv	AT candicecclay earlylifeozoneexposureresultsindysregulatedinnateimmunefunctionandalteredmicrornaexpressioninairwayepithelium AT kinjalmaniarhew earlylifeozoneexposureresultsindysregulatedinnateimmunefunctionandalteredmicrornaexpressioninairwayepithelium AT joanegerriets earlylifeozoneexposureresultsindysregulatedinnateimmunefunctionandalteredmicrornaexpressioninairwayepithelium AT theodoretwang earlylifeozoneexposureresultsindysregulatedinnateimmunefunctionandalteredmicrornaexpressioninairwayepithelium AT edwardmpostlethwait earlylifeozoneexposureresultsindysregulatedinnateimmunefunctionandalteredmicrornaexpressioninairwayepithelium AT michaeljevans earlylifeozoneexposureresultsindysregulatedinnateimmunefunctionandalteredmicrornaexpressioninairwayepithelium AT justinhfontaine earlylifeozoneexposureresultsindysregulatedinnateimmunefunctionandalteredmicrornaexpressioninairwayepithelium AT lisaamiller earlylifeozoneexposureresultsindysregulatedinnateimmunefunctionandalteredmicrornaexpressioninairwayepithelium
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Early life ozone exposure results in dysregulated innate immune function and altered microRNA expression in airway epithelium.

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