{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T18:09:01Z","timestamp":1775153341871,"version":"3.50.1"},"reference-count":53,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,11,19]],"date-time":"2015-11-19T00:00:00Z","timestamp":1447891200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000145","name":"Alberta Innovates - Health Solutions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000145","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2015,12]]},"abstract":"Summary<\/jats:title>Background<\/jats:title>Proteinase\u2010activated receptor 2 (PAR<\/jats:styled-content>2<\/jats:sub>) is a G protein\u2010coupled receptor activated by trypsin\u2010like serine proteinases. PAR<\/jats:styled-content>2<\/jats:sub> activation has been associated with inflammation including allergic airway inflammation. We have also shown that PAR<\/jats:styled-content>2<\/jats:sub> activation in the airways leads to allergic sensitization. The exact contribution of PAR<\/jats:styled-content>2<\/jats:sub> in the development of eosinophilic inflammation and airway hyperresponsiveness (AHR<\/jats:styled-content>) in sensitized individuals is not clear.<\/jats:p><\/jats:sec>Objective<\/jats:title>To investigate whether functional inhibition of PAR<\/jats:styled-content>2<\/jats:sub> during allergen challenge of allergic mice would inhibit allergen\u2010induced AHR<\/jats:styled-content> and inflammation in mouse models of asthma.<\/jats:p><\/jats:sec>Methods<\/jats:title>Mice were sensitized and challenged with ovalbumin (OVA<\/jats:styled-content>) or cockroach extract (CE<\/jats:styled-content>). To investigate the role of PAR<\/jats:styled-content>2<\/jats:sub> in the development of AHR<\/jats:styled-content> and airway inflammation, we administered blocking anti\u2010PAR<\/jats:styled-content>2<\/jats:sub> antibodies, or a cell permeable peptide inhibitor of PAR<\/jats:styled-content>2<\/jats:sub> signalling, pepducin, i.n. before allergen challenges and then assessed AHR<\/jats:styled-content> and airway inflammation.<\/jats:p><\/jats:sec>Results<\/jats:title>Administration of anti\u2010PAR<\/jats:styled-content>2<\/jats:sub> antibodies significantly inhibited OVA<\/jats:styled-content>\u2010 and CE<\/jats:styled-content>\u2010induced AHR<\/jats:styled-content> and airway inflammation. In particular, two anti\u2010PAR<\/jats:styled-content>2<\/jats:sub> antibodies, the monoclonal SAM<\/jats:styled-content>\u201011 and polyclonal B5, inhibited AHR<\/jats:styled-content>, airway eosinophilia, the increase of cytokines in the lung tissue and antigen\u2010specific T cell proliferation, but had no effect on antigen\u2010specific IgG and IgE levels. Pepducin was also effective in inhibiting AHR<\/jats:styled-content> and airway inflammation in an OVA<\/jats:styled-content> model of allergic airway inflammation.<\/jats:p><\/jats:sec>Conclusions and Clinical Relevance<\/jats:title>Functional blockade of PAR<\/jats:styled-content>2<\/jats:sub> in the airways during allergen challenge improves allergen\u2010induced AHR<\/jats:styled-content> and inflammation in mice. Therefore, topical PAR<\/jats:styled-content>2<\/jats:sub> blockade in the airways, through anti\u2010PAR<\/jats:styled-content>2<\/jats:sub> antibodies or molecules that interrupt PAR<\/jats:styled-content>2<\/jats:sub> signalling, has the potential to be used as a therapeutic option in allergic asthma.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.12628","type":"journal-article","created":{"date-parts":[[2015,8,27]],"date-time":"2015-08-27T15:05:18Z","timestamp":1440687918000},"page":"1844-1855","source":"Crossref","is-referenced-by-count":55,"title":["Functional inhibition of PAR<\/scp>2<\/sub> alleviates allergen\u2010induced airway hyperresponsiveness and inflammation"],"prefix":"10.1111","volume":"45","author":[{"given":"M.","family":"Asaduzzaman","sequence":"first","affiliation":[{"name":"Pulmonary Research Group Department of Medicine University of Alberta Edmonton AB Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Nadeem","sequence":"additional","affiliation":[{"name":"Pulmonary Research Group Department of Medicine University of Alberta Edmonton AB Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Arizmendi","sequence":"additional","affiliation":[{"name":"Pulmonary Research Group Department of Medicine University of Alberta Edmonton AB Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Davidson","sequence":"additional","affiliation":[{"name":"Pulmonary Research Group Department of Medicine University of Alberta Edmonton AB Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. 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