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The Role of Proteinase Activated Receptor-2 (PAR-2) Activation in the Airways
- Author / Creator
- Fiteih, Yahya Muhammad
Allergens possessing serine proteinase activity like house dust mite (HDM) and cockroach can activate proteinase-activated receptor-2 (PAR-2), a pro-inflammatory G-coupled receptor.
Par-2 -/- mice develop attenuated airway inflammation compared to WT mice. PAR-2 blockage in the airways abrogated the ability of CD4+ T cells to transfer the disease to naïve mice, decreased lung Th2 cytokines, and decreased ex vivo splenocyte proliferation in response to HDM. As a result, activation of PAR-2 is critical for allergic sensitization and allergic airway inflammation. Inhibiting PAR-2 activation in the airways is interesting, although cells mediating PAR-2 activation in the airways and the role of PAR-2 activation on the formation of CD4+ T memory cells are not fully understood.
Using mouse models, we demonstrated that PAR-2 activation in the airways induce the release of inflammatory mediators essential for Th2 skewing of the immune response. In addition, the loss of PAR-2 expression on airway structural cells, possibly airway epithelium attenuates allergic airway inflammation. Moreover, we have evidence indicating that the loss of PAR-2 expression abrogated the ability of CD4+ T cells to transfer the disease to naïve mice. Furthermore, we propose that the loss of PAR-2 expression attenuates the formation of CD4+ T memory cells in the lung and spleens of mice treated with house dust mite (HDM).
We hypothesize that the loss of PAR-2 expression on structural cells, such as airway epithelium, suppresses the production of inflammatory mediators necessary for Th2 polarization of the immune response, resulting in a decrease in CD4 + T memory cells in the lung and spleen.
Our study is highlighting the critical role of PAR-2 activation on airway structural cells and its role on memory cells formation. PAR-2 antagonists, or the neutralisation of mediators released after PAR-2 activation, could be a very appealing therapeutic approach for preventing asthmatic airway inflammation. The capacity to apply targeted therapeutic techniques will be enhanced if the involvement of airway epithelial cells can be determined.
- Subjects / Keywords
- Graduation date
- Spring 2022
- Type of Item
- Master of Science
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