{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:09:22Z","timestamp":1790719762526,"version":"4.1.0"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2017,4,12]],"date-time":"2017-04-12T00:00:00Z","timestamp":1491955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0174913","type":"journal-article","created":{"date-parts":[[2017,4,12]],"date-time":"2017-04-12T18:40:56Z","timestamp":1492022456000},"page":"e0174913","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":17,"title":["Human neutrophil peptide-1 promotes alcohol-induced hepatic fibrosis and hepatocyte apoptosis"],"prefix":"10.1371","volume":"12","author":[{"given":"Rie","family":"Ibusuki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6976-7483","authenticated-orcid":true,"given":"Hirofumi","family":"Uto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Oda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Ohshige","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuaki","family":"Tabu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiichi","family":"Mawatari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotaro","family":"Kumagai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Kanmura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Tamai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Moriuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirohito","family":"Tsubouchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Ido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2017,4,12]]},"reference":[{"key":"ref1","author":"P CH","year":"1952"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1016\/S0140-6736(09)60746-7","article-title":"Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders","volume":"373","author":"J Rehm","year":"2009","journal-title":"Lancet"},{"key":"ref3","first-page":"174","article-title":"Global alcohol-attributable deaths from cancer, liver cirrhosis, and injury in 2010","volume":"35","author":"J Rehm","year":"2013","journal-title":"Alcohol Res"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/hep.23258","article-title":"Alcoholic liver disease","volume":"51","author":"RS O'Shea","year":"2010","journal-title":"Hepatology"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1053\/j.gastro.2011.09.002","article-title":"Alcoholic liver disease: pathogenesis and new therapeutic targets","volume":"141","author":"B Gao","year":"2011","journal-title":"Gastroenterology"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1053\/j.gastro.2005.11.016","article-title":"Predicting cirrhosis risk based on the level of circulating hepatitis B viral load","volume":"130","author":"UH Iloeje","year":"2006","journal-title":"Gastroenterology"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/S0168-8278(03)00004-7","article-title":"A comparison in the progression of liver fibrosis in chronic hepatitis C between persistently normal and elevated transaminase","volume":"38","author":"CK Hui","year":"2003","journal-title":"J Hepatol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/S0168-8278(00)00089-1","article-title":"Hepatocyte apoptosis is a pathologic feature of human alcoholic hepatitis","volume":"34","author":"S Natori","year":"2001","journal-title":"J Hepatol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1002\/hep.510300604","article-title":"Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis","volume":"30","author":"P Angulo","year":"1999","journal-title":"Hepatology"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0962-8924(00)88932-1","article-title":"The role of DNA fragmentation in apoptosis","volume":"5","author":"CD Bortner","year":"1995","journal-title":"Trends Cell Biol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0741-8329(02)00206-9","article-title":"Neutrophilic infiltration in alcoholic hepatitis","volume":"27","author":"AP Bautista","year":"2002","journal-title":"Alcohol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0741-8329(02)00200-8","article-title":"Neutrophil-mediated tissue injury in alcoholic hepatitis","volume":"27","author":"H Jaeschke","year":"2002","journal-title":"Alcohol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1080\/10915810490502069","article-title":"Early-phase alcoholic liver disease: an update on animal models, pathology, and pathogenesis","volume":"23","author":"S Ramaiah","year":"2004","journal-title":"Int J Toxicol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1002\/jlb.61.6.647","article-title":"Mechanisms of neutrophil-induced parenchymal cell injury","volume":"61","author":"H. Jaeschke","year":"1997","journal-title":"J. Leukocyte Biol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/j.jchromb.2010.03.014","article-title":"Validation of a quantitative assay for human neutrophil peptide-1, -2, and -3 in human plasma and serum by liquid chromatography coupled to tandem mass spectrometry","volume":"878","author":"I van den Broek","year":"2010","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.1110\/ps.062336606","article-title":"Crystal structures of human alpha-defensins HNP4, HD5, and HD6","volume":"15","author":"A Szyk","year":"2006","journal-title":"Protein Sci"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1172\/JCI112121","article-title":"Primary structures of three human neutrophil defensins","volume":"76","author":"ME Selsted","year":"1985","journal-title":"J Clin Invest"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1002\/ibd.20854","article-title":"Human neutrophil peptides 1\u20133 are useful biomarkers in patients with active ulcerative colitis","volume":"15","author":"S Kanmura","year":"2009","journal-title":"Inflamm Bowel Dis"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1002\/ibd.21855","article-title":"Human neutrophil peptide-1 aggravates dextran sulfate sodium-induced colitis","volume":"18","author":"S Hashimoto","year":"2012","journal-title":"Inflamm Bowel Dis"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/cmi.2014.2","article-title":"The role of neutrophils in the development of liver diseases","volume":"11","author":"R Xu","year":"2014","journal-title":"Cell Mol Immunol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.clinre.2011.07.005","article-title":"Therapeutic strategies for severe alcoholic hepatitis","volume":"35","author":"Y Horie","year":"2011","journal-title":"Clin Res Hepatol Gastroenterol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/S0025-6196(24)00530-5","article-title":"Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease","volume":"55","author":"J Ludwig","year":"1980","journal-title":"Mayo Clin Proc"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1111\/liv.12203","article-title":"Transgenic expression of human neutrophil peptide-1 enhances hepatic fibrosis in mice fed a choline-deficient, L-amino acid-defined diet","volume":"33","author":"R Ibusuki","year":"2013","journal-title":"Liver Int"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.alcohol.2012.08.004","article-title":"Rodent models of alcoholic liver disease: Of mice and men","volume":"46","author":"Elizabeth Brandon-Warner","year":"2012","journal-title":"Alcohol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1182\/blood-2004-11-4416","article-title":"Junctional adhesion molecule-A deficiency increases hepatic ischemia-reperfusion injury despite reduction of neutrophil transendothelial migration","volume":"106","author":"Andrej Khandoga","year":"2005","journal-title":"Blood"},{"issue":"6","key":"ref26","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1016\/j.tiv.2013.05.009","article-title":"Ethanol-induced apoptosis in human liver adenocarcinoma cells (SK-Hep1): Fas- and mitochondria-mediated pathways and interaction with MAPK signaling system","volume":"27","author":"Y Morio","year":"2013","journal-title":"Toxicol In Vitro"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"G516","DOI":"10.1152\/ajpgi.00537.2010","article-title":"Innate immunity in alcoholic liver disease","volume":"300","author":"B Gao","year":"2011","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/0168-8278(90)90223-E","article-title":"Interleukin-6 release by rat liver macrophages","volume":"11","author":"KJ Busam","year":"1990","journal-title":"J Hepatol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.bbamcr.2014.11.006","article-title":"Apoptotic human neutrophil peptide-1 anti-tumor activity revealed by cellular biomechanics","volume":"1853","author":"D Gaspar","year":"2015","journal-title":"Biochim Biophys Acta"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"6901","DOI":"10.1158\/1078-0432.CCR-09-0484","article-title":"Intratumoral expression of mature human neutrophil peptide-1 mediates antitumor immunity in mice","volume":"15","author":"YS Wang","year":"2009","journal-title":"Clin Cancer Res"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1158\/1535-7163.MCT-08-0010","article-title":"Human alpha-defensin-1 inhibits growth of human lung adenocarcinoma xenograft in nude mice","volume":"7","author":"N Xu","year":"2008","journal-title":"Mol Cancer Ther"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.3892\/or.2013.2947","article-title":"Intratumoral expression of mature human neutrophil peptide-1 potentiates the therapeutic effect of doxorubicin in a mouse 4T1 breast cancer model","volume":"31","author":"D Li","year":"2014","journal-title":"Oncol Rep"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.lfs.2006.11.016","article-title":"The concentration-dependent chemokine release and pro-apoptotic effects of neutrophil-derived alpha-defensin-1 on human bronchial and alveolar epithelial cells","volume":"80","author":"CY Liu","year":"2007","journal-title":"Life Sci"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1053\/j.gastro.2014.10.042","article-title":"Gut\u2013Liver Axis in Alcoholic Liver Disease","volume":"148","author":"G Szabo","year":"2015","journal-title":"Gastroenterology"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.cyto.2008.03.002","article-title":"Granulocyte colony-stimulating factor: molecular mechanisms of action during steady state and 'emergency' hematopoiesis","volume":"42","author":"AD Panopoulos","year":"2008","journal-title":"Cytokine"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"2963","DOI":"10.4049\/jimmunol.168.6.2963","article-title":"Role of lipopolysaccharide-binding protein in early alcohol-induced liver injury in mice","volume":"168","author":"T Uesugi","year":"2002","journal-title":"J Immunol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"4737","DOI":"10.4049\/jimmunol.166.7.4737","article-title":"Reduced early alcohol-induced liver injury in CD14-deficient mice","volume":"166","author":"M Yin","year":"2001","journal-title":"J Immunol"},{"key":"ref38","first-page":"G355","article-title":"Neutrophil and Kupffer cell-induced oxidant stress and ischemia-reperfusion injury in rat liver","volume":"260","author":"H Jaeschke","year":"1991","journal-title":"Am J Physiol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"3958","DOI":"10.4049\/jimmunol.179.6.3958","article-title":"Chemoattraction of macrophages, T lymphocytes, and mast cells is evolutionarily conserved within the human alpha-defensin family","volume":"179","author":"J Grigat","year":"2007","journal-title":"J Immunol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.molcel.2007.05.010","article-title":"Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis","volume":"26","author":"TC Chang","year":"2007","journal-title":"Mol Cell"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/jcmm.12223","article-title":"The functional role of microRNAs in alcoholic liver injury","volume":"18","author":"K McDaniel","year":"2014","journal-title":"J Cell Mol Med"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.brainresbull.2009.08.006","article-title":"miR-34a, a microRNA up-regulated in a double transgenic mouse model of Alzheimer's disease, inhibits bcl2 translation","volume":"80","author":"X Wang","year":"2009","journal-title":"Brain Res Bull"},{"issue":"Suppl 1","key":"ref43","doi-asserted-by":"crossref","first-page":"E59","DOI":"10.1111\/j.1530-0277.2012.01852.x","article-title":"Chronic ethanol feeding alters miRNA expression dynamics during liver regeneration","volume":"37","author":"RP Dippold","year":"2013","journal-title":"Alcohol Clin Exp Res"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/j.ajpath.2012.06.010","article-title":"Epigenetic regulation of miR-34a expression in alcoholic liver injury","volume":"181","author":"F Meng","year":"2012","journal-title":"Am J Pathol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/sj.cdd.4401369","article-title":"hsp70-DnaJ chaperone pair prevents nitric oxide- and CHOP-induced apoptosis by inhibiting translocation of Bax to mitochondria","volume":"11","author":"T Gotoh","year":"2004","journal-title":"Cell Death Differ"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1126\/science.1190217","article-title":"BID, BIM, and PUMA are essential for activation of the BAX- and BAK-dependent cell death program","volume":"330","author":"D Ren","year":"2010","journal-title":"Science"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1053\/j.gastro.2004.07.019","article-title":"Hepatocyte-specific disruption of Bcl-xL leads to continuous hepatocyte apoptosis and liver fibrotic responses","volume":"127","author":"T Takehara","year":"2004","journal-title":"Gastroenterology"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"48S","DOI":"10.1111\/j.1530-0277.2000.tb00012.x","article-title":"Plasma endotoxin and serum cytokine levels in patients with alcoholic hepatitis: relation to severity of liver disturbance","volume":"24","author":"M Fujimoto","year":"2000","journal-title":"Alcohol Clin Exp Res"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0168-8278(88)80024-2","article-title":"Subcellular changes and apoptosis induced by ethanol in rat liver","volume":"6","author":"A Benedetti","year":"1988","journal-title":"J Hepatol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"e2491","DOI":"10.1371\/journal.pntd.0002491","article-title":"Human neutrophil peptide-1 (HNP-1): a new anti-leishmanial drug candidate","volume":"7","author":"S Dabirian","year":"2013","journal-title":"PLoS Negl Trop Dis"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1172\/JCI3664","article-title":"Antibacterial activity of human neutrophil defensins in experimental infections in mice is accompanied by increased leukocyte accumulation","volume":"102","author":"MM Welling","year":"1998","journal-title":"J Clin Invest"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1146\/annurev.iy.11.040193.000541","article-title":"Defensins: antimicrobial and cytotoxic peptides of mammalian cells","volume":"11","author":"RI Lehrer","year":"1993","journal-title":"Annu Rev Immunol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0174913","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T22:09:30Z","timestamp":1750198170000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0174913"}},"subtitle":[],"editor":[{"given":"Matias A","family":"Avila","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,4,12]]},"references-count":52,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2017,4,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0174913","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,12]]}}}