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29318.pdf (3.11 MB)
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PPAR-gamma Regulates T Cell Responses in Air Pollutant-associated Inflammation
Author Info
Kim, Dasom
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1522414820700163
Abstract Details
Year and Degree
2018, MS, University of Cincinnati, Medicine: Toxicology (Environmental Health).
Abstract
Air pollution is a global health threat and causes millions of human deaths annually. Toxic air pollutants have been associated with disrupted immune responses and inflammatory homeostasis. Pregnancy and fetal development stages are highly susceptible to environmental exposures that tend to induce deleterious inflammatory responses. Mechanistic evidence supports that air pollutants impact various cellular and molecular targets, which alter immune responses and lead to systemic diseases. Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous lipophilic air pollutants released from incomplete combustion of organic materials, such as automobile fuel-burning, industrial gas emission, cigarette smoking, and food grilling. Exposure to PAHs increases the risk of various inflammatory diseases and conditions, such as bronchitis, dermatitis, asthma, and obesity. However, whether and how PAHs interfere immune cell responses and exacerbate inflammatory diseases remains elusive. As known, dendritic cells (DCs) activate effector CD4+ and CD8+ T cells through antigen presentation and cytokine stimulation, determining the balance of pro- and anti-inflammatory responses. Thus, we hypothesize that PAH-exposed DCs alter the cytokine production of T cells, leading to an unbalanced inflammatory homeostasis. To test this hypothesis, we treated human DCs with benzo[a]pyrene (BaP), a common component of PAHs, and showed the increased production of inflammatory cytokine interferon-y (IFN-y) in DC-mediated T cell activation. To further determine which genes and pathways regulate the immune responses altered by BaP, we performed transcriptomic analysis on BaP-treated DCs and showed that BaP exposure inhibited the expression of the gene cluster mediated by the nuclear transcription factor peroxisome proliferator-activated receptor-? (PPAR-?). To test whether PPAR-? regulates the effect of PAH exposure on T cell activation and inflammatory response, we treated DCs with PPAR-? agonist (pioglitazone) and antagonist (GW9662) and measured the surface markers and intracellular cytokine production of T cells. Our results showed that DCs treated with PPAR-? antagonist increased IFN-? production from CD4+ and CD8+ T cells and DCs treated with PPAR-? agonist showed an indication of decreased IFN-? production from CD8+ T cells in response to BaP exposure. These accumulative results support that BaP exposure enhances pro-inflammatory responses, which can be partially alleviated by the activation of PPAR-? pathway. Therefore, manipulation of PPAR-? pathway provides a potential mean to regulate inflammatory diseases associated with PAH exposure.
Committee
Shouxiong Huang, Ph.D. (Committee Chair)
Aimin Chen, Ph.D. (Committee Member)
Pages
99 p.
Subject Headings
Toxicology
Keywords
Immunotoxicology
;
Environmental Health
;
Polycyclic aromatic hydrocarbons
;
Air pollution
;
PPAR gamma
Recommended Citations
Refworks
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Citations
Kim, D. (2018).
PPAR-gamma Regulates T Cell Responses in Air Pollutant-associated Inflammation
[Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1522414820700163
APA Style (7th edition)
Kim, Dasom.
PPAR-gamma Regulates T Cell Responses in Air Pollutant-associated Inflammation.
2018. University of Cincinnati, Master's thesis.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1522414820700163.
MLA Style (8th edition)
Kim, Dasom. "PPAR-gamma Regulates T Cell Responses in Air Pollutant-associated Inflammation." Master's thesis, University of Cincinnati, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1522414820700163
Chicago Manual of Style (17th edition)
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Document number:
ucin1522414820700163
Download Count:
255
Copyright Info
© 2018, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.