Proteinase-activated receptor-2 activation participates in allergic sensitization to house dust mite allergens in a murine model

• DOI: 10.1111/cea.12185
• Publication Date: 2013-08-14T07:15:47Z
• Authors: C. E. Davidson; M. Asaduzzaman; N. G. Arizmendi; D. Polley; Y. Wu; J. R. Gordon; M. D. Hollenberg; L. Cameron; H. Vliagoftis
• Keywords: CD4-Positive T-Lymphocytes; Inflammation; Male; Mice, Knockout; 0303 health sciences; Pyroglyphidae; Allergens; Lymphocyte Activation; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; Th2 Cells; Immunoglobulin G; Hypersensitivity; Animals; Cytokines; Receptor, PAR-2; Lung; Spleen

Background Many aeroallergens contain proteinase activity and are able to induce allergic sensitization when presented mucosal surfaces. Some of these allergens activate proteinase-activated receptor-2 (PAR2). Objective To determine the role PAR2 activation in a murine house dust mite (HDM) allergy model. Methods We sensitized challenged PAR2-deficient mice with HDM, examined outcomes compared wild-type animals. focus on sensitization, we administered blocking antibody animals during phase immediately after or following subsequent allergen challenge. Results found HDM failed develop airway inflammation, did not produce HDM-specific IgG1 had less IL-4 mRNA lungs than Prevention diminished levels Th2 mediators, including IL-4, IL-5 IL-13, lungs. Blocking also led decreased manifestations disease, hyperresponsiveness (AHR) inflammation HDM-induced proliferation splenocytes obtained from presence was reduced relative those that receive antibody. The effect blockade could be transferred naïve through splenic CD4+ T cells mice. Conclusions Clinical Relevance plays key our model, leading increased lung cytokine production augmented reactivity. is common mechanism for wide variety therefore potential pharmacological target prevent allergy.