{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:06:52Z","timestamp":1791936412667,"version":"4.3.4"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Neutrophils promote experimental abdominal aortic aneurysm (AAA) formation via a mechanism that is independent from MMPs (matrix metalloproteinases). Recently, we reported a dominant role of IL (interleukin)-1\u03b2 in the formation of murine experimental AAAs. Here, the hypothesis that IL-1\u03b2\u2013induced neutrophil extracellular trap formation (NETosis) promotes AAA was tested.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>NETs were identified through colocalized staining of neutrophil, Cit-H3 (citrullinated histone H3), and DNA, using immunohistochemistry. NETs were detected in human AAAs and were colocalized with IL-1\u03b2. In vitro, IL-1RA attenuated IL-1\u03b2\u2013induced NETosis in human neutrophils. Mechanistically, IL-1\u03b2 treatment of isolated neutrophils induced nuclear localization of ceramide synthase 6 and synthesis of C16-ceramide, which was inhibited by IL-1RA or fumonisin B1, an inhibitor of ceramide synthesis. Furthermore, IL-1RA or fumonisin B1 attenuated IL1-\u03b2\u2013induced NETosis. In an experimental model of murine AAA, NETs were detected at a very early stage\u2013day 3 of aneurysm induction. IL-1\u03b2\u2013knockout mice demonstrated significantly lower infiltration of neutrophils to aorta and were protected from AAA. Adoptive transfer of wild-type neutrophils promoted AAA formation in IL-1\u03b2\u2013knockout mice. Moreover, treatment of wild-type mice with Cl-amidine, an inhibitor NETosis, significantly attenuated AAA formation, whereas, treatment with deoxyribonuclease, a DNA digesting enzyme, had no effect on AAA formation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Altogether, the results suggest a dominant role of IL-1\u03b2\u2013induced NETosis in AAA formation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.117.309897","type":"journal-article","created":{"date-parts":[[2018,2,22]],"date-time":"2018-02-22T10:00:10Z","timestamp":1519293610000},"page":"843-853","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":253,"title":["Novel Role of IL (Interleukin)-1\u03b2 in Neutrophil Extracellular Trap Formation and Abdominal Aortic Aneurysms"],"prefix":"10.1161","volume":"38","author":[{"given":"Akshaya K.","family":"Meher","sequence":"first","affiliation":[{"name":"From the Department of Surgery (A.K.M., M.S., J.P.D., N.P., V.E.L., G.S., G.A., G.R.U.), Department of Pharmacology (A.K.M., V.S., N.L.), Robert M. Berne Cardiovascular Research Center (A.K.M., N.L., G.A., G.R.U.), Department of Molecular Physiology and Biological Physics (G.R.U.), and Department of Biomedical Engineering (G.A.), University of Virginia, Charlottesville."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Spinosa","sequence":"additional","affiliation":[{"name":"From the Department of Surgery (A.K.M., M.S., J.P.D., N.P., V.E.L., G.S., G.A., G.R.U.), Department of Pharmacology (A.K.M., V.S., N.L.), Robert M. Berne Cardiovascular Research Center (A.K.M., N.L., G.A., G.R.U.), Department of Molecular Physiology and Biological Physics (G.R.U.), and Department of Biomedical Engineering (G.A.), University of Virginia, Charlottesville."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Davis","sequence":"additional","affiliation":[{"name":"From the Department of Surgery (A.K.M., M.S., J.P.D., N.P., V.E.L., G.S., G.A., G.R.U.), Department of Pharmacology (A.K.M., V.S., N.L.), Robert M. Berne Cardiovascular Research Center (A.K.M., N.L., G.A., G.R.U.), Department of Molecular Physiology and Biological Physics (G.R.U.), and Department of Biomedical Engineering (G.A.), University of Virginia, Charlottesville."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Pope","sequence":"additional","affiliation":[{"name":"From the Department of Surgery (A.K.M., M.S., J.P.D., N.P., V.E.L., G.S., G.A., G.R.U.), Department of Pharmacology (A.K.M., V.S., N.L.), Robert M. Berne Cardiovascular Research Center (A.K.M., N.L., G.A., G.R.U.), Department of Molecular Physiology and Biological Physics (G.R.U.), and Department of Biomedical Engineering (G.A.), University of Virginia, Charlottesville."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor E.","family":"Laubach","sequence":"additional","affiliation":[{"name":"From the Department of Surgery (A.K.M., M.S., J.P.D., N.P., V.E.L., G.S., G.A., G.R.U.), Department of Pharmacology (A.K.M., V.S., N.L.), Robert M. Berne Cardiovascular Research Center (A.K.M., N.L., G.A., G.R.U.), Department of Molecular Physiology and Biological Physics (G.R.U.), and Department of Biomedical Engineering (G.A.), University of Virginia, Charlottesville."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Su","sequence":"additional","affiliation":[{"name":"From the Department of Surgery (A.K.M., M.S., J.P.D., N.P., V.E.L., G.S., G.A., G.R.U.), Department of Pharmacology (A.K.M., V.S., N.L.), Robert M. Berne Cardiovascular Research Center (A.K.M., N.L., G.A., G.R.U.), Department of Molecular Physiology and Biological Physics (G.R.U.), and Department of Biomedical Engineering (G.A.), University of Virginia, Charlottesville."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vlad","family":"Serbulea","sequence":"additional","affiliation":[{"name":"From the Department of Surgery (A.K.M., M.S., J.P.D., N.P., V.E.L., G.S., G.A., G.R.U.), Department of Pharmacology (A.K.M., V.S., N.L.), Robert M. Berne Cardiovascular Research Center (A.K.M., N.L., G.A., G.R.U.), Department of Molecular Physiology and Biological Physics (G.R.U.), and Department of Biomedical Engineering (G.A.), University of Virginia, Charlottesville."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Leitinger","sequence":"additional","affiliation":[{"name":"From the Department of Surgery (A.K.M., M.S., J.P.D., N.P., V.E.L., G.S., G.A., G.R.U.), Department of Pharmacology (A.K.M., V.S., N.L.), Robert M. Berne Cardiovascular Research Center (A.K.M., N.L., G.A., G.R.U.), Department of Molecular Physiology and Biological Physics (G.R.U.), and Department of Biomedical Engineering (G.A.), University of Virginia, Charlottesville."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gorav","family":"Ailawadi","sequence":"additional","affiliation":[{"name":"From the Department of Surgery (A.K.M., M.S., J.P.D., N.P., V.E.L., G.S., G.A., G.R.U.), Department of Pharmacology (A.K.M., V.S., N.L.), Robert M. Berne Cardiovascular Research Center (A.K.M., N.L., G.A., G.R.U.), Department of Molecular Physiology and Biological Physics (G.R.U.), and Department of Biomedical Engineering (G.A.), University of Virginia, Charlottesville."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Gilbert R.","family":"Upchurch","sequence":"additional","affiliation":[{"name":"From the Department of Surgery (A.K.M., M.S., J.P.D., N.P., V.E.L., G.S., G.A., G.R.U.), Department of Pharmacology (A.K.M., V.S., N.L.), Robert M. 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