{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:42:58Z","timestamp":1790685778026,"version":"4.1.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2009,5,1]],"date-time":"2009-05-01T00:00:00Z","timestamp":1241136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Korea Research Foundation","doi-asserted-by":"crossref","award":["2007\u2013521-E00052"],"award-info":[{"award-number":["2007\u2013521-E00052"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>\u03b3-Secretase inhibitor (GSI) has been used to effectively block Notch signaling, which is implicated in the differentiation and functional regulation of T helper (Th) effector cells. In asthma, a subset of CD4+ T cells is believed to initiate and perpetuate the disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The aim of this study was to evaluate the therapeutic potential of GSI against allergic asthma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>GSI was administered to an ovalbumin-sensitized mouse via an intranasal route at the time of ovalbumin challenge.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>The administration of GSI inhibits asthma phenotypes, including eosinophilic airway inflammation, goblet cell metaplasia, methacholine-induced airway hyperresponsiveness, and serum IgE production. GSI treatment of bronchoalveolar lavage cells stimulated via TCR or non-TCR pathways led to a decrease in Th2 cytokine production with a concomitant increase in Th1 cytokine secretion. Expression of Hes-1, a target of Notch signaling, was down-regulated in conjunction with a reduction of Notch intracellular domain and GATA-3 levels after GSI treatment of bronchoalveolar lavage cells. GSI treatment resulted in an inhibition of NF-\u03baB activation, and combined treatment with GSI and an NF-\u03baB inhibitor augmented IFN-\u03b3 production in a synergistic manner.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These data suggest that GSI directly regulates Th1 and Th2 responses in allergic pulmonary inflammation through a Notch signaling\u2013dependent pathway and that GSI is of high therapeutic value for treating asthma by inhibiting airway inflammatory responses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.200806-893oc","type":"journal-article","created":{"date-parts":[[2009,2,21]],"date-time":"2009-02-21T22:37:16Z","timestamp":1235255836000},"page":"875-882","source":"Crossref","is-referenced-by-count":91,"title":["\u03b3-Secretase Inhibitor Reduces Allergic Pulmonary Inflammation by Modulating Th1 and Th2 Responses"],"prefix":"10.1093","volume":"179","author":[{"given":"Jin Hyun","family":"Kang","sequence":"first","affiliation":[{"name":"Division of Molecular and Life Sciences, College of Science and Technology, Hanyang University, Seoul"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Molecular and Life Sciences, College of Science and Technology, Hanyang University, Seoul"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Gi","family":"Uhm","sequence":"additional","affiliation":[{"name":"Division of Molecular and Life Sciences, College of Science and Technology, Hanyang University, Seoul"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-Hwa","family":"Lee","sequence":"additional","affiliation":[{"name":"Genome Research Center for Allergy and Respiratory Diseases, Division of Allergy and Respiratory Medicine, Soonchunhyang University Hospital, Bucheon; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gap Ryol","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Life Science, Sogang University, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choon-Sik","family":"Park","sequence":"additional","affiliation":[{"name":"Genome Research Center for Allergy and Respiratory Diseases, Division of Allergy and Respiratory Medicine, Soonchunhyang University Hospital, Bucheon; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Il Yup","family":"Chung","sequence":"additional","affiliation":[{"name":"Division of Molecular and Life Sciences, College of Science and Technology, Hanyang University, 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