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Protease-activated receptor-2 activation contributes to house dust mite-induced IgE responses in mice.
PLoS One 2014; 9(3):e91206Plos

Abstract

Aeroallergens such as house dust mite (HDM), cockroach, and grass or tree pollen are innocuous substances that can induce allergic sensitization upon inhalation. The serine proteases present in these allergens are thought to activate the protease-activated receptor (PAR)-2, on the airway epithelium, thereby potentially inducing allergic sensitization at the expense of inhalation tolerance. We hypothesized that the proteolytic activity of allergens may play an important factor in the allergenicity to house dust mite and is essential to overcome airway tolerance. Here, we aimed to investigate the role of PAR-2 activation in allergic sensitization and HDM-induced allergic airway inflammation. In our study, Par-2 deficient mice were treated with two different HDM extracts containing high and low serine protease activities twice a week for a period of 5 weeks. We determined airway inflammation through quantification of percentages of mononuclear cells, eosinophils and neutrophils in the bronchial alveolar lavage fluid and measured total IgE and HDM-specific IgE and IgG1 levels in serum. Furthermore, Th2 and pro-inflammatory cytokines including IL-5, IL-13, Eotaxin-1, IL-17, KC, Chemokine (C-C motif) ligand 17 (CCL17) and thymic stromal lymphopoietin (TSLP), were measured in lung tissue homogenates. We observed that independent of the serine protease content, HDM was able to induce elevated levels of eosinophils and neutrophils in the airways of both wild-type (WT) and Par-2 deficient mice. Furthermore, we show that induction of pro-inflammatory cytokines by HDM exposure is independent of Par-2 activation. In contrast, serine protease activity of HDM does contribute to enhanced levels of total IgE, but not HDM-specific IgE. We conclude that, while Par-2 activation contributes to the development of IgE responses, it is largely dispensable for the HDM-induced induction of pro-inflammatory cytokines and airway inflammation in an experimental mouse model of HDM-driven allergic airway disease.

Authors+Show Affiliations

Lab. Allergology & Pulmonary Diseases, Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.Lab. Allergology & Pulmonary Diseases, Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.Lab. Allergology & Pulmonary Diseases, Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.Lab. Allergology & Pulmonary Diseases, Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.Lab. Allergology & Pulmonary Diseases, Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.Lab. Allergology & Pulmonary Diseases, Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24651123

Citation

Post, Sijranke, et al. "Protease-activated Receptor-2 Activation Contributes to House Dust Mite-induced IgE Responses in Mice." PloS One, vol. 9, no. 3, 2014, pp. e91206.
Post S, Heijink IH, Petersen AH, et al. Protease-activated receptor-2 activation contributes to house dust mite-induced IgE responses in mice. PLoS ONE. 2014;9(3):e91206.
Post, S., Heijink, I. H., Petersen, A. H., de Bruin, H. G., van Oosterhout, A. J., & Nawijn, M. C. (2014). Protease-activated receptor-2 activation contributes to house dust mite-induced IgE responses in mice. PloS One, 9(3), pp. e91206. doi:10.1371/journal.pone.0091206.
Post S, et al. Protease-activated Receptor-2 Activation Contributes to House Dust Mite-induced IgE Responses in Mice. PLoS ONE. 2014;9(3):e91206. PubMed PMID: 24651123.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protease-activated receptor-2 activation contributes to house dust mite-induced IgE responses in mice. AU - Post,Sijranke, AU - Heijink,Irene H, AU - Petersen,Arjen H, AU - de Bruin,Harold G, AU - van Oosterhout,Antoon J M, AU - Nawijn,Martijn C, Y1 - 2014/03/20/ PY - 2013/02/13/received PY - 2014/02/10/accepted PY - 2014/3/22/entrez PY - 2014/3/22/pubmed PY - 2014/12/23/medline SP - e91206 EP - e91206 JF - PloS one JO - PLoS ONE VL - 9 IS - 3 N2 - Aeroallergens such as house dust mite (HDM), cockroach, and grass or tree pollen are innocuous substances that can induce allergic sensitization upon inhalation. The serine proteases present in these allergens are thought to activate the protease-activated receptor (PAR)-2, on the airway epithelium, thereby potentially inducing allergic sensitization at the expense of inhalation tolerance. We hypothesized that the proteolytic activity of allergens may play an important factor in the allergenicity to house dust mite and is essential to overcome airway tolerance. Here, we aimed to investigate the role of PAR-2 activation in allergic sensitization and HDM-induced allergic airway inflammation. In our study, Par-2 deficient mice were treated with two different HDM extracts containing high and low serine protease activities twice a week for a period of 5 weeks. We determined airway inflammation through quantification of percentages of mononuclear cells, eosinophils and neutrophils in the bronchial alveolar lavage fluid and measured total IgE and HDM-specific IgE and IgG1 levels in serum. Furthermore, Th2 and pro-inflammatory cytokines including IL-5, IL-13, Eotaxin-1, IL-17, KC, Chemokine (C-C motif) ligand 17 (CCL17) and thymic stromal lymphopoietin (TSLP), were measured in lung tissue homogenates. We observed that independent of the serine protease content, HDM was able to induce elevated levels of eosinophils and neutrophils in the airways of both wild-type (WT) and Par-2 deficient mice. Furthermore, we show that induction of pro-inflammatory cytokines by HDM exposure is independent of Par-2 activation. In contrast, serine protease activity of HDM does contribute to enhanced levels of total IgE, but not HDM-specific IgE. We conclude that, while Par-2 activation contributes to the development of IgE responses, it is largely dispensable for the HDM-induced induction of pro-inflammatory cytokines and airway inflammation in an experimental mouse model of HDM-driven allergic airway disease. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/24651123/Protease_activated_receptor_2_activation_contributes_to_house_dust_mite_induced_IgE_responses_in_mice_ L2 - http://dx.plos.org/10.1371/journal.pone.0091206 DB - PRIME DP - Unbound Medicine ER -