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

  • Allergic airway inflammation

• Graduation date

  Spring 2022

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-tbax-d761

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.