{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T21:53:59Z","timestamp":1784843639858,"version":"3.55.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2012,3,1]],"date-time":"2012-03-01T00:00:00Z","timestamp":1330560000000},"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":[[2012,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>The role of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) in the development or progression of interstitial lung disease (ILD) is controversial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate the association between statin use and ILD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used regression analyses to evaluate the association between statin use and interstitial lung abnormalities (ILA) in a large cohort of smokers from COPDGene. Next, we evaluated the effect of statin pretreatment on bleomycin-induced fibrosis in mice and explored the mechanism behind these observations in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>In COPDGene, 38% of subjects with ILA were taking statins compared with 27% of subjects without ILA. Statin use was positively associated in ILA (odds ratio, 1.60; 95% confidence interval, 1.03\u20132.50; P = 0.04) after adjustment for covariates including a history of high cholesterol or coronary artery disease. This association was modified by the hydrophilicity of statin and the age of the subject. Next, we demonstrate that statin administration aggravates lung injury and fibrosis in bleomycin-treated mice. Statin pretreatment enhances caspase-1\u2013mediated immune responses in vivo and in vitro; the latter responses were abolished in bone marrow\u2013derived macrophages isolated from Nlrp3\u2212\/\u2212 and Casp1\u2212\/\u2212 mice. Finally, we provide further insights by demonstrating that statins enhance NLRP3-inflammasome activation by increasing mitochondrial reactive oxygen species generation in macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Statin use is associated with ILA among smokers in the COPDGene study and enhances bleomycin-induced lung inflammation and fibrosis in the mouse through a mechanism involving enhanced NLRP3-inflammasome activation. Our findings suggest that statins may influence the susceptibility to, or progression of, ILD.<\/jats:p>\n                    <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT 00608764).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201108-1574oc","type":"journal-article","created":{"date-parts":[[2012,1,13]],"date-time":"2012-01-13T02:25:44Z","timestamp":1326421544000},"page":"547-556","source":"Crossref","is-referenced-by-count":125,"title":["Statins and Pulmonary Fibrosis: The Potential Role of NLRP3 Inflammasome Activation"],"prefix":"10.1093","volume":"185","author":[{"given":"Jin-Fu","family":"Xu","sequence":"first","affiliation":[{"name":"Pulmonary and Critical Care Division"},{"name":"Department of Pulmonary Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George R.","family":"Washko","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiichi","family":"Nakahira","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroto","family":"Hatabu","sequence":"additional","affiliation":[{"name":"Center for Pulmonary Functional Imaging"},{"name":"Department of Radiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avignat S.","family":"Patel","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isis E.","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizuki","family":"Nishino","sequence":"additional","affiliation":[{"name":"Center for Pulmonary Functional Imaging"},{"name":"Department of Radiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Okajima","sequence":"additional","affiliation":[{"name":"Department of Radiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuneo","family":"Yamashiro","sequence":"additional","affiliation":[{"name":"Center for Pulmonary Functional Imaging"},{"name":"Department of Radiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Ross","sequence":"additional","affiliation":[{"name":"Surgical Planning Laboratory, Department of Radiology"},{"name":"Channing Laboratory, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ra\u00fal","family":"San Jos\u00e9 Est\u00e9par","sequence":"additional","affiliation":[{"name":"Department of Radiology"},{"name":"Surgical Planning Laboratory, Department of Radiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro A.","family":"Diaz","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division"},{"name":"Department of Pulmonary Diseases, Pontificia Universidad Cat\u00f3lica de Chile, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Ping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie-Ming","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Huadong Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanca E.","family":"Himes","sequence":"additional","affiliation":[{"name":"Channing Laboratory, and"},{"name":"Center for Genomic Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn E.","family":"Come","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"D'Aco","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division"},{"name":"Channing Laboratory, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando J.","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; 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