Degree

Doctor of Philosophy (PhD)

Department

Comparative Biomedical Sciences

Document Type

Dissertation

Abstract

Up to 44% of students in the U.S. and 67% in the Eastern Mediterranean regions use the waterpipe (hookah). Research evaluating potential adverse respiratory effects arising from either indirect waterpipe tobacco smoke (WTS) exposures due to prenatal exposures or direct exposures as adults are limited. We hypothesized that prenatal exposures to WTS aggravate adult lung immune responses to house dust mite (HDM) allergen and adult exposures to WTS impairs lung function and alters lung immune responses. To investigate these hypotheses, pregnant BALB/c dams were exposed to either air or WTS for 2 hours per day during gestational days 6 to 19. Beginning at 14 and 15 weeks of age, male and female offspring were given intranasal instillations of saline or HDM once per week for 3 weeks. For adult exposures, male and female BALB/c mice were exposed to either air or WTS for 1 hour per day for 21 consecutive days, or 2 hours a day for 48 consecutive days. Lung function, bronchoalveolar lavage fluid (BALF), and lung tissue were then examined.

Prenatal WTS exposure alone resulted in significant downregulation of genes in adult offspring. Histopathology revealed phenotypic asthmatic changes in both HDM-challenged male groups. Prenatal WTS + HDM males had significantly higher levels of BALF neutrophils and increased expression of Il-13, Il-21, Mip-1b/Ccl4, and Eotaxin/Ccl11. Prenatal WTS + HDM females had upregulated Ccl26, GM-CSF/Csf2, Il-17a, and Il-25/Il-17e levels, yet only the prenatal air + HDM females displayed phenotypic asthmatic responses. Adult WTS exposures resulted in dysregulated levels of lung xenobiotic and immune response genes, with increased expression of Ahrr, Cyp1a1, and Cyp1b1, downregulation of Ifng, Il-6, Il-10, and Il-13, significantly higher BALF neutrophils, and higher cellularity, lymphocyte, and neutrophil scores.

Overall, these data support our hypotheses that 1) maternal waterpipe smoking places offspring at risk for long-term health issues, suggesting a sex-specific initiation of immunosuppressive effects in the lungs that persist into adulthood and modification of lung immune responses to a common respiratory allergen; and that 2) WTS exposure interferes with normal lung function and immune processes, activating xenobiotic metabolism and suppressing immune cell communication via differential cytokine regulation.

Date

5-10-2020

Committee Chair

Penn, Arthur

Available for download on Friday, May 07, 2027

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