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

Autor: Edward M. Postlethwait, Candice C. Clay, Theodore T. Wang, Joan E. Gerriets, Kinjal Maniar-Hew, Lisa A. Miller, Michael J. Evans, Justin H. Fontaine
Přispěvatelé: Kalinichenko, Vladimir V
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Lipopolysaccharides
Male
Anatomy and Physiology
Pulmonology
Lipopolysaccharide
Fluorescent Antibody Technique
Toxicology
Epithelium
chemistry.chemical_compound
0302 clinical medicine
Immune Physiology
Innate
2.1 Biological and endogenous factors
Aetiology
Lung
3' Untranslated Regions
Cells
Cultured
0303 health sciences
Multidisciplinary
Cultured
Animal Models
Innate Immunity
3. Good health
medicine.anatomical_structure
Respiratory
Cytokines
Medicine
Epigenetics
Macaque
Research Article
Protein Binding
Biotechnology
General Science & Technology
Science
Cells
Immunology
Pediatric Pulmonology
Biology
Proinflammatory cytokine
03 medical and health sciences
Model Organisms
Immune system
Ozone
medicine
Genetics
Animals
Humans
Interleukin 8
Interleukin 6
030304 developmental biology
Innate immune system
Interleukin-6
Gene Expression Profiling
Interleukin-8
Immunity
Epithelial Cells
Newborn
Macaca mulatta
Immunity
Innate
MicroRNAs
Animals
Newborn
030228 respiratory system
chemistry
Gene Expression Regulation
13. Climate action
Immune System
biology.protein
Respiratory epithelium
Clinical Immunology
Zdroj: Clay, CC; Maniar-Hew, K; Gerriets, JE; Wang, TT; Postlethwait, EM; Evans, MJ; et al.(2014). Early life ozone exposure results in dysregulated innate immune function and altered microRNA expression in airway epithelium. PLoS ONE, 9(3). doi: 10.1371/journal.pone.0090401. UC Davis: Retrieved from: http://www.escholarship.org/uc/item/37h4v507
PloS one, vol 9, iss 3
PLoS ONE, Vol 9, Iss 3, p e90401 (2014)
PLoS ONE
DOI: 10.1371/journal.pone.0090401.
Popis: 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 39 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. ©Clay et al.
Databáze: OpenAIRE
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