{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:56:45Z","timestamp":1791014205423,"version":"4.1.0"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2011,7,1]],"date-time":"2011-07-01T00:00:00Z","timestamp":1309478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cathepsin S (Cat S) is predominantly expressed in antigen-presenting cells and is up-regulated in several preclinical models of antigen-induced inflammation, suggesting a role in the allergic response. Prophylactic dosing of an irreversible Cat S inhibitor has been shown to attenuate pulmonary eosinophilia in mice, supporting the hypothesis that Cat S inhibition before the initiation of airway inflammation is beneficial in airway disease. In addition, Cat S has been shown to play a role in more distal events in the allergic response. To determine where Cat S inhibition may affect the allergic response, we used complementary genetic and pharmacological approaches to investigate the role of Cat S in the early and downstream allergic events in a murine model of antigen-induced lung inflammation. Cat S knockout mice did not develop ovalbumin-induced pulmonary inflammation, consistent with a role for Cat S in the development of the allergic response. Alternatively, wild-type mice were treated with a reversible, highly selective Cat S inhibitor in prophylactic and therapeutic dosing paradigms and assessed for changes in airway inflammation. Although both treatment paradigms resulted in potent Cat S inhibition, only prophylactic Cat S inhibitor dosing blocked lung inflammation, consistent with our findings in Cat S knockout mice. The findings indicate that although Cat S is up-regulated in allergic models, it does not appear to play a significant role in the downstream effector inflammatory phase in this model; however, our results demonstrate that Cat S inhibition in a prophylactic paradigm would ameliorate airway inflammation.<\/jats:p>","DOI":"10.1165\/rcmb.2009-0392oc","type":"journal-article","created":{"date-parts":[[2010,9,21]],"date-time":"2010-09-21T00:42:33Z","timestamp":1285029753000},"page":"81-87","source":"Crossref","is-referenced-by-count":40,"title":["Genetic and Pharmacological Evaluation of Cathepsin S in a Mouse Model of Asthma"],"prefix":"10.1093","volume":"45","author":[{"given":"Kathleen","family":"Deschamps","sequence":"first","affiliation":[{"name":"In Vivo Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanda","family":"Cromlish","sequence":"additional","affiliation":[{"name":"In vitro Sciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Weicker","sequence":"additional","affiliation":[{"name":"In Vivo Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Lamontagne","sequence":"additional","affiliation":[{"name":"In vitro Sciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah L.","family":"Huszar","sequence":"additional","affiliation":[{"name":"In Vivo Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques Yves","family":"Gauthier","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, Kirkland, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Mudgett","sequence":"additional","affiliation":[{"name":"Genetically Engineered Models Department, Merck Research Laboratories, Rahway, New Jersey; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Guimond","sequence":"additional","affiliation":[{"name":"The Mouse Clinical Institute, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Romand","sequence":"additional","affiliation":[{"name":"The Mouse Clinical Institute, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelly","family":"Frossard","sequence":"additional","affiliation":[{"name":"The Mouse Clinical Institute, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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