Year of Award
2026
Document Type
Thesis
Degree Type
Master of Science (MS)
Degree Name
Toxicology
Department or School/College
BMED/CEHS
Committee Chair
Andrij Holian
Committee Co-chair
Christopher Migliaccio
Commitee Members
Zeina Jaffar, Ethan Walker
Keywords
Sex Difference, Innate Immune Response, Woodsmoke, Lung Function, Female mice
Subject Categories
Toxicology
Abstract
With the increased prevalence of wildfires, understanding the long-term health effects of exposure to wood smoke (WS) is of obvious importance. Epidemiological studies report increased hospital admissions and deaths during wildfire events, but the long term and subclinical health effects have not been characterized. In order to examine potentialmechanisms contributing to long term health impacts WS exposure studies were conducted using a murine In a murine model of wildfire smoke exposure, delayed decreases in lung function following environmentally relevant WS exposure were observed only in males. To elucidate the potential contribution of estrogen to the sex bias, female mice were treated with fulvestrant, an estrogen receptor antagonist prior to and during WS exposures. In addition to lung function assessment, ex vivo lung tissue samples were assessed for oxidative stress, inflammatory response, and markers of epithelial mesenchymal transition. While there were no WS-induced changes to lung function infulvestrant-treated females, sex differences were observed in alveolar macrophage (AM) functions and phenotype. Analysis of AMs revealed a higher basal Nrf2 activation level in females and immune precursors to EMT in the lung tissue of males. In vitro studies mirrored WS induced gene and protein expression observed in males in vivo, serving as a proof of concept for an in vitro model of the pathological pulmonary immune response to WS. The results suggest that a higher basal level of redox scavengers in the female lung have a protective effect and macrophage driven EMT may be attributable to the decrease in lung function observed in males. These studies contribute to defining the mechanism of sex as a biological variable on WS-induced adverse health effects.
Recommended Citation
SEX DIFFERENCES IN THE INNATE IMMUNE RESPONSE TO WOODSMOKE PROTECT LUNG FUNCTION IN FEMALE MICE
© Copyright 2026 Madison Grace Miller