Journal Article Ppublish 3 citations
PubMed: 39716873 DOI: 10.1152/ajplung.00332.2024
Evidence of sex differences in ozone-induced oxysterol and cytokine levels in differentiated human nasal epithelial cells.
Am J Physiol Lung Cell Mol Physiol 328(2):L207-L214
Authors: Dre'Von A Dobson, Alexia Perryman, Erin McNell, Hye-Young H Kim, Ned A Porter, Meghan E Rebuli, Ilona Jaspers
Affiliations
- Curriculum in Toxicology and Environmental Medicine, University of North Carolina at Chapel Hill, North Carolina, United States.
- Department of Chemistry and Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee, United States.
- Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina at Chapel Hill, North Carolina, United States.
- Department of Pediatrics, University of North Carolina at Chapel Hill, North Carolina, United States.
Abstract
Acute exposure to ozone (O 3) causes upper and lower airway inflammation. We and others have previously demonstrated that O 3 oxidizes lipids, particularly cholesterol, into electrophilic oxysterols, such as secosterol B (SecoB), which can adduct proteins, thus altering cellular signaling pathways. To investigate how O 3-derived oxysterols influence cytokine and chemokine release, nasal epithelial cells (HNECs) from healthy donors (n = 18 donors) were exposed to 0.4 ppm O 3 for 4 h. Afterward, immune mediators in apical washes and basolateral supernatants were analyzed using ELISAs, whereas sterol and oxysterol levels were examined using liquid-chromatography mass spectrometry (LC-MS). O 3 exposure increased SecoB, 7-ketocholesterol (7Keto-Chol), 27-hydroxycholesterol (27OH-Chol), and epoxycholesterols in a sex-dependent manner. Female-derived HNECs had significant increases in SecoB, 27OH-Chol, and β-epoxycholesterol, whereas male-derived cells showed increases in 7Keto-Chol only. O 3 decreased the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-7 but increased interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), VEGF, and Eotaxin. Females exhibited O 3-induced IL-1β and VEGF increases, whereas males showed increased Eotaxin and reduced GM-CSF. Basolaterally, O 3 exposure decreased GM-CSF and thymus and activation-regulated chemokine (TARC) while raising IL-6, IL-13, IL-1β, IL-8, and TNFα. Females showed higher TNFα and IL-1β, but males did not. Oxysterols correlated differently with cytokines by sex. Females showed positive correlations between oxysterols and proinflammatory cytokines like IL-6 and IL-1β, whereas males displayed negative correlations with IL-6, IL-8, and TNFα. In conclusion, O 3-induced cytokine/chemokine responses and sterol/oxysterol levels in HNECs vary by sex, with donor-specific oxysterols associated with O 3-triggered inflammatory mediator release.NEW & NOTEWORTHY It is increasingly recognized that lung biology and responses to pollutant exposures differ in males and females. Using a model of differentiated nasal epithelial cells from male and female donors, our data demonstrate that pollutant-induced cytokine/chemokine responses and oxidized lipid levels vary by sex, with donor-specific oxidized lipids linked to inflammatory mediator release.
MeSH
Chemokine Ccl17, Cytokines, Cells, Granulocyte-Macrophage Colony-Stimulating Factor, Oxysterols, Chemokines, Environmental Pollutants, Epithelial Cells, Interleukin-6, Interleukin-8, Sterols, Cholesterol, Sex Characteristics, Sex, Sex Differences