BACKGROUND: Proteinase-activated receptors (PAR)-2 are members of the family of G-protein-coupled receptors activated by proteases. These receptors are widely expressed in several tissues and in virtually all cells involved in rhinitis and asthma. In particular, proteinases activating PAR-2 may affect airway functions and play a role in human diseases. OBJECTIVE: Assessment of the role of PAR-2 in bronchoconstriction, airway responsiveness and immune response after allergic challenge, in rabbits sensitized to Par j 1, the major allergen of Parietaria judaica pollen. METHODS: Evaluation of antigen challenge in rabbits treated with PAR-2-activating peptide (PAR-2AP) (SLIGRL) or the scrambled peptide LSIGRL or vehicle immediately before allergen exposure measuring airway responsiveness. Characterization of bronchoalveolar lavage (BAL) following histamine challenge and phenotype analysis of cells by flow cytometry and analysis of cytokine production by quantitative PCR. RESULTS: PAR-2AP pre-treatment, but not the scrambled peptide, was able to significantly inhibit bronchoconstriction, airway hyper-responsiveness and to modulate the immune response induced by allergic challenge in sensitized rabbits. The phenotype analysis of the cells recovered from BAL showed an increase in RLA-DR-positive cells while RTLA-positive cells were unchanged. IFN-gamma and IL-2 production were inhibited, with a concomitant increase in IL-10 of about 10-fold over the control values. CONCLUSIONS: In this experimental model, PAR-2 modulates bronchoconstriction interfering with antigen challenge-induced immune response in rabbits sensitized and challenged to Par j 1.
BACKGROUND: Proteinase-activated receptors (PAR)-2 are members of the family of G-protein-coupled receptors activated by proteases. These receptors are widely expressed in several tissues and in virtually all cells involved in rhinitis and asthma. In particular, proteinases activating PAR-2 may affect airway functions and play a role in human diseases. OBJECTIVE: Assessment of the role of PAR-2 in bronchoconstriction, airway responsiveness and immune response after allergic challenge, in rabbits sensitized to Par j 1, the major allergen of Parietaria judaica pollen. METHODS: Evaluation of antigen challenge in rabbits treated with PAR-2-activating peptide (PAR-2AP) (SLIGRL) or the scrambled peptide LSIGRL or vehicle immediately before allergen exposure measuring airway responsiveness. Characterization of bronchoalveolar lavage (BAL) following histamine challenge and phenotype analysis of cells by flow cytometry and analysis of cytokine production by quantitative PCR. RESULTS: PAR-2AP pre-treatment, but not the scrambled peptide, was able to significantly inhibit bronchoconstriction, airway hyper-responsiveness and to modulate the immune response induced by allergic challenge in sensitized rabbits. The phenotype analysis of the cells recovered from BAL showed an increase in RLA-DR-positive cells while RTLA-positive cells were unchanged. IFN-gamma and IL-2 production were inhibited, with a concomitant increase in IL-10 of about 10-fold over the control values. CONCLUSIONS: In this experimental model, PAR-2 modulates bronchoconstriction interfering with antigen challenge-induced immune response in rabbits sensitized and challenged to Par j 1.
Authors: Koa Hosoki; Allan R Brasier; Alexander Kurosky; Istvan Boldogh; Sanjiv Sur Journal: Am J Respir Cell Mol Biol Date: 2017-02 Impact factor: 6.914
Authors: Paul C Porter; Tianshu Yang; Amber Luong; George L Delclos; Stuart L Abramson; Farrah Kheradmand; David B Corry Journal: Biochim Biophys Acta Date: 2011-06-25
Authors: Heddie L Nichols; Mahmoud Saffeddine; Barbara S Theriot; Akhil Hegde; Daniel Polley; Tamer El-Mays; Harissios Vliagoftis; Morley D Hollenberg; Emma H Wilson; Julia K L Walker; Kathryn A DeFea Journal: Proc Natl Acad Sci U S A Date: 2012-09-25 Impact factor: 11.205
Authors: Paul Porter; Sumanth Polikepahad; Yuping Qian; J Morgan Knight; Wen Lu; Wendy M-T Tai; Luz Roberts; Valentine Ongeri; Tianshu Yang; Alexander Seryshev; Stuart Abramson; George L Delclos; Farrah Kheradmand; David B Corry Journal: Med Mycol Date: 2010-08-31 Impact factor: 4.076