{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:03:13Z","timestamp":1791388993962,"version":"4.3.3"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2005,11,1]],"date-time":"2005-11-01T00:00:00Z","timestamp":1130803200000},"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":[[2005,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Emphysema is one of the major pathological abnormalities associated with chronic obstructive pulmonary disease. The protease\/antiprotease imbalance and inflammation resulting from oxidative stress have been attributed to the pathogenesis of emphysema. Nrf2 is believed to protect against oxidative tissue damage through the transcriptional activation of a battery of antioxidant enzymes. In this study, we investigated the protective role of Nrf2 in the development of emphysema using elastase-induced emphysema as our model system. We found that elastase-provoked emphysema was markedly exacerbated in Nrf2-knockout (KO) mice compared with wild-type mice. The severity of emphysema in Nrf2-KO mice correlated intimately with the degree of lung inflammation in the initial stage of elastase treatment. The highly inducible expression of antioxidant and antiprotease genes observed in wild-type alveolar macrophages was significantly attenuated in the lungs of Nrf2-KO mice. Interestingly, transplantation of wild-type bone marrow cells into Nrf2-KO mice retarded the development of initial lung inflammation and subsequent emphysema, and this improvement correlated well with the appearance of macrophages expressing Nrf2-regulated antiprotease and antioxidant genes. Thus, Nrf2 appears to exert its protective effects through the transcriptional activation of antiprotease and antioxidant genes in alveolar macrophages.<\/jats:p>","DOI":"10.4049\/jimmunol.175.10.6968","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T00:57:58Z","timestamp":1398041878000},"page":"6968-6975","source":"Crossref","is-referenced-by-count":221,"title":["Transcription Factor Nrf2 Plays a Pivotal Role in Protection against Elastase-Induced Pulmonary Inflammation and Emphysema"],"prefix":"10.1093","volume":"175","author":[{"given":"Yukio","family":"Ishii","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, University of Tsukuba , Tsukuba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Itoh","sequence":"additional","affiliation":[{"name":"Exploratory Research for Advanced Technology (ERATO) Environmental Response Project, University of Tsukuba , Tsukuba ,","place":["Japan"]},{"name":"Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, University of Tsukuba , Tsukuba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Morishima","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, University of Tsukuba , Tsukuba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, University of Tsukuba , Tsukuba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Kiwamoto","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, University of Tsukuba , Tsukuba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"IIzuka","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, University of Tsukuba , Tsukuba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed E","family":"Hegab","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, University of Tsukuba , Tsukuba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonori","family":"Hosoya","sequence":"additional","affiliation":[{"name":"Exploratory Research for Advanced Technology (ERATO) Environmental Response Project, University of Tsukuba , Tsukuba ,","place":["Japan"]},{"name":"Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, University of Tsukuba , Tsukuba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Nomura","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, University of Tsukuba , Tsukuba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tohru","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, University of Tsukuba , Tsukuba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Exploratory Research for Advanced Technology (ERATO) Environmental Response Project, University of Tsukuba , Tsukuba ,","place":["Japan"]},{"name":"Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, University of Tsukuba , Tsukuba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyohisa","family":"Sekizawa","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, University of Tsukuba , Tsukuba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2005,11,15]]},"reference":[{"key":"2025032808573530000_R1","first-page":"1498","volume-title":"Lancet","year":"1997"},{"key":"2025032808573530000_R2","first-page":"269","volume-title":"N. 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