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The role of the inflammasome in the ...
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Bauer, Rebecca N.
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The role of the inflammasome in the respiratory innate immune response to viruses and pollutants: Insights for asthma pathogenesis.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
The role of the inflammasome in the respiratory innate immune response to viruses and pollutants: Insights for asthma pathogenesis./
作者:
Bauer, Rebecca N.
出版者:
Ann Arbor : ProQuest Dissertations & Theses, : 2014,
面頁冊數:
248 p.
附註:
Source: Dissertation Abstracts International, Volume: 75-09(E), Section: B.
Contained By:
Dissertation Abstracts International75-09B(E).
標題:
Environmental health. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3622301
ISBN:
9781303939518
The role of the inflammasome in the respiratory innate immune response to viruses and pollutants: Insights for asthma pathogenesis.
Bauer, Rebecca N.
The role of the inflammasome in the respiratory innate immune response to viruses and pollutants: Insights for asthma pathogenesis.
- Ann Arbor : ProQuest Dissertations & Theses, 2014 - 248 p.
Source: Dissertation Abstracts International, Volume: 75-09(E), Section: B.
Thesis (Ph.D.)--The University of North Carolina at Chapel Hill, 2014.
This item is not available from ProQuest Dissertations & Theses.
The respiratory mucosal innate immune system is composed of both structural cells, such as airway epithelial cells, and immune cells, such as macrophages, that together determine the appropriate immune response to inhaled stimuli. These cells use pattern recognition receptors to distinguish between harmless and harmful stimuli by recognizing conserved microbial pathogen-associated molecular patterns (PAMPs) and endogenously derived damage-associated molecular patterns (DAMPs) from damaged tissue. Inappropriate immune responses to normally innocuous stimuli underpin the pathogenesis of a number of immune disorders, including asthma, a chronic inflammatory disease of the airway typified by difficulty breathing in response to a trigger. In this dissertation, we explored the contribution of the inflammasome signaling complex to respiratory mucosal host defense against two sources of asthma exacerbation: influenza A virus infection and inhalation of the oxidant air pollutant ozone (O3). The inflammasome is an innate immune complex composed of a pattern recognition receptor, the protease caspase-1, and an adaptor protein (PYCARD) that when formed induces activation of caspase-1-mediated processing of the pro-inflammatory mediators IL-1beta and IL-18 or cell death. Our results show that caspase-1 and the inflammasome contribute to the airway epithelial cell innate immune response to influenza and that this pathway is modified by asthma, suggesting a role for caspase-1 in virus-induced asthma exacerbation. Using a mouse model of allergic airway inflammation, we also show that caspase-1 may be involved in the development of allergic asthma, though its function in asthma development is complex. In the context of O3, we found increased presence of several DAMPs that may activate inflammasome signaling in the airway of healthy volunteers exposed to O3, but no evidence to suggest that inflammasome signaling strongly contributes to the innate immune response to O3. Finally, we identified a mechanism by which O3 alters the interaction between epithelial cells and macrophages leading to the accumulation of DAMPs that may activate innate immune responses in the lung. In summary, our results shed light on the function of the inflammasome in the human respiratory innate immune response to viruses and pollutants, and provide insight on the contribution of inflammasome signaling to asthma pathogenesis.
ISBN: 9781303939518Subjects--Topical Terms:
543032
Environmental health.
The role of the inflammasome in the respiratory innate immune response to viruses and pollutants: Insights for asthma pathogenesis.
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The respiratory mucosal innate immune system is composed of both structural cells, such as airway epithelial cells, and immune cells, such as macrophages, that together determine the appropriate immune response to inhaled stimuli. These cells use pattern recognition receptors to distinguish between harmless and harmful stimuli by recognizing conserved microbial pathogen-associated molecular patterns (PAMPs) and endogenously derived damage-associated molecular patterns (DAMPs) from damaged tissue. Inappropriate immune responses to normally innocuous stimuli underpin the pathogenesis of a number of immune disorders, including asthma, a chronic inflammatory disease of the airway typified by difficulty breathing in response to a trigger. In this dissertation, we explored the contribution of the inflammasome signaling complex to respiratory mucosal host defense against two sources of asthma exacerbation: influenza A virus infection and inhalation of the oxidant air pollutant ozone (O3). The inflammasome is an innate immune complex composed of a pattern recognition receptor, the protease caspase-1, and an adaptor protein (PYCARD) that when formed induces activation of caspase-1-mediated processing of the pro-inflammatory mediators IL-1beta and IL-18 or cell death. Our results show that caspase-1 and the inflammasome contribute to the airway epithelial cell innate immune response to influenza and that this pathway is modified by asthma, suggesting a role for caspase-1 in virus-induced asthma exacerbation. Using a mouse model of allergic airway inflammation, we also show that caspase-1 may be involved in the development of allergic asthma, though its function in asthma development is complex. In the context of O3, we found increased presence of several DAMPs that may activate inflammasome signaling in the airway of healthy volunteers exposed to O3, but no evidence to suggest that inflammasome signaling strongly contributes to the innate immune response to O3. Finally, we identified a mechanism by which O3 alters the interaction between epithelial cells and macrophages leading to the accumulation of DAMPs that may activate innate immune responses in the lung. In summary, our results shed light on the function of the inflammasome in the human respiratory innate immune response to viruses and pollutants, and provide insight on the contribution of inflammasome signaling to asthma pathogenesis.
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