{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:25:35Z","timestamp":1790162735302,"version":"4.1.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2008,10,1]],"date-time":"2008-10-01T00:00:00Z","timestamp":1222819200000},"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":[[2008,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>High-mobility group box 1 (HMGB1) is a potent inflammatory mediator elevated in sepsis and rheumatoid arthritis, although its role in cystic fibrosis (CF) lung disease is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To determine whether HMGB1 contributes to CF lung inflammation, including neutrophil chemotaxis and lung matrix degradation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used sputum and serum from subjects with CF and a Scnn1b-transgenic (Scnn1b-Tg) mouse model that overexpresses \u03b2-epithelial Na+ channel in airways and mimics the CF phenotype, including lung inflammation. Human secretions and murine bronchoalveolar lavage fluid (BALF) was assayed for HMGB1 by Western blot and ELISA. Neutrophil chemotaxis was measured in vitro after incubation with human neutrophils. The collagen fragment proline-glycine-proline (PGP) was measured by tandem mass spectroscopy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>HMGB1 was detected in CF sputum at higher levels than secretions from normal individuals. Scnn1b-Tg mice had elevated levels of HMGB1 by Western blot and ELISA. We demonstrated that dose-dependent chemotaxis of human neutrophils stimulated by purified HMGB1 was partially dependent on CXC chemokine receptors and that this could be duplicated in CF sputum and BALF from Scnn1b-Tg mice. Neutralization by anti-HMGB1 antibody, in both the sputum and BALF-reduced chemotaxis, which suggested that HMGB1 contributed to the chemotactic properties of these samples. Intratracheal administration of purified HMGB1 induced neutrophil influx into the airways of mice and promoted the release of PGP. PGP was also elevated in Scnn1b-Tg mice and CF serum.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HMGB1 expression contributes to pulmonary inflammation and lung matrix degradation in CF airway disease and deserves further investigation as a biomarker and potential therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.200712-1894oc","type":"journal-article","created":{"date-parts":[[2008,7,24]],"date-time":"2008-07-24T22:06:08Z","timestamp":1216937168000},"page":"822-831","source":"Crossref","is-referenced-by-count":95,"title":["Potential Role of High-Mobility Group Box 1 in Cystic Fibrosis Airway Disease"],"prefix":"10.1093","volume":"178","author":[{"given":"Steven M.","family":"Rowe","sequence":"first","affiliation":[{"name":"Departments of Medicine"},{"name":"Pediatrics"},{"name":"Physiology and Biophysics, and"},{"name":"Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia L.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Physiology and Biophysics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Liu","sequence":"additional","affiliation":[{"name":"Departments of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathew","family":"Hardison","sequence":"additional","affiliation":[{"name":"Physiology and Biophysics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Livraghi","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis\/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Martin","family":"Solomon","sequence":"additional","affiliation":[{"name":"Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Brent","family":"McQuaid","sequence":"additional","affiliation":[{"name":"Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett D.","family":"Noerager","sequence":"additional","affiliation":[{"name":"Physiology and Biophysics, and"},{"name":"Department of Biology, Chemistry, and Mathematics, University of Montevallo, Montevallo, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Gaggar","sequence":"additional","affiliation":[{"name":"Departments of Medicine"},{"name":"Physiology and Biophysics, and"},{"name":"Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. P.","family":"Clancy","sequence":"additional","affiliation":[{"name":"Pediatrics"},{"name":"Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanda","family":"O'Neal","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis\/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J.","family":"Sorscher","sequence":"additional","affiliation":[{"name":"Departments of Medicine"},{"name":"Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Abraham","sequence":"additional","affiliation":[{"name":"Departments of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Edwin","family":"Blalock","sequence":"additional","affiliation":[{"name":"Physiology and Biophysics, and"},{"name":"Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,10,15]]},"reference":[{"key":"2026032102320193300_BIB1","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1126\/science.285.5425.248","volume":"285","year":"1999","journal-title":"Science"},{"key":"2026032102320193300_BIB2","doi-asserted-by":"crossref","first-page":"2950","DOI":"10.4049\/jimmunol.165.6.2950","volume":"165","year":"2000","journal-title":"J Immunol"},{"key":"2026032102320193300_BIB3","doi-asserted-by":"crossref","first-page":"L958","DOI":"10.1152\/ajplung.00359.2004","volume":"288","year":"2005","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026032102320193300_BIB4","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1093\/embo-reports\/kvf198","volume":"3","year":"2002","journal-title":"EMBO Rep"},{"key":"2026032102320193300_BIB5","doi-asserted-by":"crossref","first-page":"5551","DOI":"10.1093\/emboj\/cdg516","volume":"22","year":"2003","journal-title":"EMBO J"},{"key":"2026032102320193300_BIB6","doi-asserted-by":"crossref","first-page":"7370","DOI":"10.1074\/jbc.M306793200","volume":"279","year":"2004","journal-title":"J Biol Chem"},{"key":"2026032102320193300_BIB7","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nri1594","volume":"5","year":"2005","journal-title":"Nat Rev Immunol"},{"key":"2026032102320193300_BIB8","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/nature00858","volume":"418","year":"2002","journal-title":"Nature"},{"key":"2026032102320193300_BIB9","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1111\/j.1365-2796.2003.01302.x","volume":"255","year":"2004","journal-title":"J Intern Med"},{"key":"2026032102320193300_BIB10","doi-asserted-by":"crossref","first-page":"C1318","DOI":"10.1152\/ajpcell.00616.2005","volume":"291","year":"2006","journal-title":"Am J Physiol Cell Physiol"},{"key":"2026032102320193300_BIB11","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1053\/gast.2002.35391","volume":"123","year":"2002","journal-title":"Gastroenterology"},{"key":"2026032102320193300_BIB12","doi-asserted-by":"crossref","first-page":"105","DOI":"10.2119\/2006-00010.Yang","volume":"12","year":"2006","journal-title":"Mol Med"},{"key":"2026032102320193300_BIB13","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1007\/s00268-005-0369-2","volume":"30","year":"2006","journal-title":"World J Surg"},{"key":"2026032102320193300_BIB14","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1164\/rccm.200605-699OC","volume":"174","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032102320193300_BIB15","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1073\/pnas.2434651100","volume":"101","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026032102320193300_BIB16","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1002\/art.11161","volume":"48","year":"2003","journal-title":"Arthritis Rheum"},{"key":"2026032102320193300_BIB17","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.rdc.2004.04.007","volume":"30","year":"2004","journal-title":"Rheum Dis Clin North Am"},{"key":"2026032102320193300_BIB18","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1056\/NEJMra043184","volume":"352","year":"2005","journal-title":"N Engl J Med"},{"key":"2026032102320193300_BIB19","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/S0140-6736(03)12567-6","volume":"361","year":"2003","journal-title":"Lancet"},{"key":"2026032102320193300_BIB20","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1385\/CRIAI:23:1:041","volume":"23","year":"2002","journal-title":"Clin Rev Allergy Immunol"},{"key":"2026032102320193300_BIB21","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/nm1028","volume":"10","year":"2004","journal-title":"Nat Med"},{"key":"2026032102320193300_BIB22","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/nm1361","volume":"12","year":"2006","journal-title":"Nat Med"},{"key":"2026032102320193300_BIB23","first-page":"229","volume":"42","year":"2007","journal-title":"Pediatr Pulmonol Suppl"},{"key":"2026032102320193300_BIB24","first-page":"A448","volume":"175","year":"2007","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032102320193300_BIB25","doi-asserted-by":"crossref","first-page":"L96","DOI":"10.1152\/ajplung.00492.2006","volume":"293","year":"2007","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026032102320193300_BIB26","doi-asserted-by":"crossref","first-page":"6601","DOI":"10.4049\/jimmunol.167.11.6601","volume":"167","year":"2001","journal-title":"J Immunol"},{"key":"2026032102320193300_BIB27","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1373\/49.9.1535","volume":"49","year":"2003","journal-title":"Clin Chem"},{"key":"2026032102320193300_BIB28","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1189\/jlb.0703340","volume":"75","year":"2004","journal-title":"J Leukoc Biol"},{"key":"2026032102320193300_BIB29","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1161\/01.CIR.0000142050.19488.C7","volume":"110","year":"2004","journal-title":"Circulation"},{"key":"2026032102320193300_BIB30","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/S0022-3476(98)70344-0","volume":"132","year":"1998","journal-title":"J Pediatr"},{"key":"2026032102320193300_BIB31","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1056\/NEJM199409083311003","volume":"331","year":"1994","journal-title":"N Engl J Med"},{"key":"2026032102320193300_BIB32","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1080\/01926230601060025","volume":"35","year":"2007","journal-title":"Toxicol Pathol"},{"key":"2026032102320193300_BIB33","first-page":"1","volume":"78","year":"2005","journal-title":"J Leukoc Biol"},{"key":"2026032102320193300_BIB34","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1016\/j.bmc.2007.01.011","volume":"15","year":"2007","journal-title":"Bioorg Med Chem"},{"key":"2026032102320193300_BIB35","doi-asserted-by":"crossref","first-page":"5662","DOI":"10.4049\/jimmunol.180.8.5662","volume":"180","year":"2008","journal-title":"J Immunol"},{"key":"2026032102320193300_BIB36","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1189\/jlb.0306196","volume":"81","year":"2007","journal-title":"J Leukoc Biol"},{"key":"2026032102320193300_BIB37","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.1002\/art.10540","volume":"46","year":"2002","journal-title":"Arthritis Rheum"},{"key":"2026032102320193300_BIB38","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1038\/sj.emboj.7601552","volume":"26","year":"2007","journal-title":"EMBO J"},{"key":"2026032102320193300_BIB39","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.4049\/jimmunol.180.4.2531","volume":"180","year":"2008","journal-title":"J Immunol"},{"key":"2026032102320193300_BIB40","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1056\/NEJMoa043891","volume":"354","year":"2006","journal-title":"N Engl J Med"},{"key":"2026032102320193300_BIB41","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1056\/NEJM200007273430407","volume":"343","year":"2000","journal-title":"N Engl J Med"},{"key":"2026032102320193300_BIB42","doi-asserted-by":"crossref","first-page":"6931","DOI":"10.4049\/jimmunol.175.10.6931","volume":"175","year":"2005","journal-title":"J Immunol"},{"key":"2026032102320193300_BIB43","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/ppul.20165","volume":"39","year":"2005","journal-title":"Pediatr Pulmonol"},{"key":"2026032102320193300_BIB44","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.jpeds.2004.06.054","volume":"145","year":"2004","journal-title":"J Pediatr"},{"key":"2026032102320193300_BIB45","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1164\/rccm.200306-731OC","volume":"168","year":"2003","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032102320193300_BIB46","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1136\/thorax.56.4.306","volume":"56","year":"2001","journal-title":"Thorax"},{"key":"2026032102320193300_BIB47","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1513\/pats.200703-038BR","volume":"4","year":"2007","journal-title":"Proc Am Thorac Soc"},{"key":"2026032102320193300_BIB48","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1513\/pats.200703-040BR","volume":"4","year":"2007","journal-title":"Proc Am Thorac Soc"},{"key":"2026032102320193300_BIB49","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1165\/rcmb.2004-0124TR","volume":"31","year":"2004","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026032102320193300_BIB50","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1513\/pats.200703-044BR","volume":"4","year":"2007","journal-title":"Proc Am Thorac Soc"},{"key":"2026032102320193300_BIB51","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1136\/adc.2004.069419","volume":"91","year":"2006","journal-title":"Arch Dis Child"},{"key":"2026032102320193300_BIB52","first-page":"125","volume":"28","year":"2005","journal-title":"Ped Pulmonol Suppl"},{"key":"2026032102320193300_BIB53","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/ni1457","volume":"8","year":"2007","journal-title":"Nat Immunol"},{"key":"2026032102320193300_BIB54","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1189\/jlb.0306200","volume":"81","year":"2007","journal-title":"J Leukoc Biol"},{"key":"2026032102320193300_BIB55","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/1465-9921-6-49","volume":"6","year":"2005","journal-title":"Respir Res"},{"key":"2026032102320193300_BIB56","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1471-2334-6-4","volume":"6","year":"2006","journal-title":"BMC Infect Dis"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/178\/8\/822\/67444991\/ajrccm_178_8_822.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/178\/8\/822\/67444991\/ajrccm_178_8_822.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T06:32:13Z","timestamp":1774074733000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/178\/8\/822\/8525974"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10]]},"references-count":56,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2008,10,15]]},"published-print":{"date-parts":[[2008,10,15]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.200712-1894oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2008,10]]},"published":{"date-parts":[[2008,10]]}}}