{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T10:18:26Z","timestamp":1777889906559,"version":"3.51.4"},"reference-count":45,"publisher":"SAGE Publications","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["VES"],"published-print":{"date-parts":[[2020,12,16]]},"abstract":"<jats:p>OBJECTIVE: This study aimed to investigate the underlying pathogenesis of acute unilateral vestibulopathy (AUV) using gene expression profiling combined with bioinformatics analysis. METHODS: Total RNA was extracted from the peripheral blood mononuclear cells of ten AUV patients in the acute phase and from ten controls. The differentially expressed genes (DEGs) between these two groups were screened using microarray analysis with the cut-off criteria (|fold changes|\u200a&gt;\u200a1.5 and p-value\u200a&lt;\u200a0.05). Functional enrichment analysis of DEGs was performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, and the protein-protein interaction (PPI) network was constructed using the STRING (Search Tool for the Retrieval of Interacting Genes) database. RESULTS: There were 57 DEGs (50 up-regulated and 7 down-regulated) identified in the AUV group. Functional enrichment analysis showed that most of the up-regulated DEGs were significantly enriched in terms related to the neutrophil-mediated immune pathway. From the PPI network, the top ten hub genes were extracted by calculating four topological properties, and most of them were related to the innate immune system, inflammatory processes and vascular disorders. The complete blood count tests showed that the neutrophil-to-lymphocyte ratio was significantly higher in the 72 AUV patients than in the age-matched controls (2.93\u00b12.25 vs 1.54\u00b10.61, p\u200a&lt;\u200a0.001). CONCLUSIONS: This study showed that the neutrophil-mediated immune pathway may contribute to the development of AUV by mediating inflammatory and thrombotic changes in the vestibular organ.<\/jats:p>","DOI":"10.3233\/ves-200044","type":"journal-article","created":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T16:50:59Z","timestamp":1606841459000},"page":"363-374","source":"Crossref","is-referenced-by-count":15,"title":["Neutrophil-mediated immune response as a possible mechanism of acute unilateral vestibulopathy"],"prefix":"10.1177","volume":"30","author":[{"given":"Eun Hye","family":"Oh","sequence":"first","affiliation":[{"name":"Department of Neurology, Pusan National University School of Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Je-Keun","family":"Rhee","sequence":"additional","affiliation":[{"name":"School of Systems Biomedical Science, Soongsil University, Seoul, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-Hong","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Pusan National University School of Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Wook","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Neurology, Pusan National University School of Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dae-Seong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology, Pusan National University School of Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Yun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seo Young","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Biomedical Research Institute, Busan, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwang-Dong","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Biomedical Research Institute, Busan, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae-Hwan","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Pusan National University School of Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","reference":[{"key":"10.3233\/VES-200044_ref1","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1097\/WCO.0000000000000649","article-title":"Peripheral vestibular disorders: an update","volume":"32","author":"Strupp","year":"2019","journal-title":"Curr Opin Neurol"},{"key":"10.3233\/VES-200044_ref2","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.ncl.2015.04.012","article-title":"Acute Unilateral Vestibulopathy","volume":"33","author":"Strupp","year":"2015","journal-title":"Neurol Clin"},{"key":"10.3233\/VES-200044_ref3","doi-asserted-by":"crossref","first-page":"459048","DOI":"10.1155\/2014\/459048","article-title":"Is vestibular neuritis an immune related vestibular neuropathy inducing vertigo?","volume":"2014","author":"Greco","year":"2014","journal-title":"J Immunol Res"},{"key":"10.3233\/VES-200044_ref4","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1212\/WNL.55.6.880","article-title":"Detection of herpes simplex virus type 1 in human vestibular nuclei","volume":"55","author":"Arbusow","year":"2000","journal-title":"Neurology"},{"key":"10.3233\/VES-200044_ref5","doi-asserted-by":"crossref","first-page":"93","DOI":"10.3109\/00016489509121878","article-title":"Herpetic vestibular neuritis: an experimental study","volume":"519","author":"Hirata","year":"1995","journal-title":"Acta Otolaryngol Suppl"},{"key":"10.3233\/VES-200044_ref6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/00034894810900S101","article-title":"Clerf Lecture Vestibular neuritis","volume":"90","author":"Schuknecht","year":"1981","journal-title":"Ann Otol Rhinol Laryngol Suppl"},{"key":"10.3233\/VES-200044_ref7","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1159\/000320839","article-title":"Proinflammatory activation of peripheral blood mononuclear cells in patients with vestibular neuritis","volume":"16","author":"Kassner","year":"2011","journal-title":"Audiol Neurootol"},{"key":"10.3233\/VES-200044_ref8","doi-asserted-by":"crossref","first-page":"E257","DOI":"10.1002\/lary.25204","article-title":"The significance of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in vestibular neuritis","volume":"125","author":"Chung","year":"2015","journal-title":"Laryngoscope"},{"key":"10.3233\/VES-200044_ref9","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jocn.2019.05.062","article-title":"Mean platelet volume, neutrophil- and platelet to lymphocyte ratios are elevated in vestibular neuritis","volume":"67","author":"\u015eahin","year":"2019","journal-title":"J Clin Neurosci"},{"key":"10.3233\/VES-200044_ref10","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1177\/0003489417718846","article-title":"Cardiovascular Risk Factors Among Patients With Vestibular Neuritis","volume":"126","author":"Oron","year":"2017","journal-title":"Ann Otol Rhinol Laryngol"},{"key":"10.3233\/VES-200044_ref12","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1038\/s41598-020-58947-y","article-title":"CNN3 acts as a potential oncogene in cervical cancer by affecting RPLP1 mRNA expression","volume":"10","author":"Xia","year":"2020","journal-title":"Sci Rep"},{"key":"10.3233\/VES-200044_ref13","doi-asserted-by":"crossref","first-page":"e0222952","DOI":"10.1371\/journal.pone.0222952","article-title":"Concordance between gene expression in peripheral whole blood and colonic tissue in children with inflammatory bowel disease","volume":"14","author":"Palmer","year":"2019","journal-title":"PLoS One"},{"key":"10.3233\/VES-200044_ref14","doi-asserted-by":"crossref","first-page":"372","DOI":"10.3109\/14397595.2015.1091136","article-title":"Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were useful markers in assessment of inflammatory response and disease activity in SLE patients","volume":"26","author":"Qin","year":"2016","journal-title":"Mod Rheumatol"},{"key":"10.3233\/VES-200044_ref15","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s10072-014-1912-4","article-title":"Incidence, seasonality and comorbidity in vestibular neuritis","volume":"36","author":"Adamec","year":"2015","journal-title":"Neurol Sci"},{"key":"10.3233\/VES-200044_ref16","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.chom.2014.04.011","article-title":"The balancing act of neutrophils","volume":"15","author":"Bardoel","year":"2014","journal-title":"Cell Host Microbe"},{"key":"10.3233\/VES-200044_ref17","doi-asserted-by":"crossref","first-page":"216592","DOI":"10.1155\/2012\/216592","article-title":"Acute-phase inflammatory response in idiopathic sudden deafness: pathogenic implications","volume":"2012","author":"Lopez-Gonzalez","year":"2012","journal-title":"Int J Otolaryngol"},{"key":"10.3233\/VES-200044_ref18","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.jbspin.2011.12.012","article-title":"A genetic association study of the CLEC12A gene in rheumatoid arthritis","volume":"79","author":"Michou","year":"2012","journal-title":"Joint Bone Spine"},{"key":"10.3233\/VES-200044_ref19","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1186\/s13018-017-0674-0","article-title":"A time-course microarray data analysis reveals consistent dysregulated genes and upstream microRNAs in autoantibody-mediated arthritis","volume":"12","author":"Wang","year":"2017","journal-title":"J Orthop Surg Res"},{"key":"10.3233\/VES-200044_ref20","doi-asserted-by":"crossref","first-page":"908","DOI":"10.3109\/14397595.2015.1024302","article-title":"Association of IL-1R2 genetic polymorphisms with the susceptibility of ankylosing spondylitis in Northern Chinese Han population","volume":"25","author":"Xia","year":"2015","journal-title":"Mod Rheumatol"},{"key":"10.3233\/VES-200044_ref21","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1080\/03009740600704221","article-title":"SLC11A1 gene polymorphisms in Korean patients with Behcet\u2019s disease","volume":"35","author":"Kim","year":"2006","journal-title":"Scand J Rheumatol"},{"key":"10.3233\/VES-200044_ref22","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1080\/08820139.2017.1296857","article-title":"Matrix Metalloproteinase-9 rs6 Gene Polymorphism and Behcet\u2019s Disease: Is There an Association?","volume":"46","author":"Kamal","year":"2017","journal-title":"Immunol Invest"},{"key":"10.3233\/VES-200044_ref23","doi-asserted-by":"crossref","first-page":"35802","DOI":"10.1038\/srep35802","article-title":"Genetic analysis of innate immunity in Behcet\u2019s disease identifies an association with IL-37 and IL-18RAP","volume":"6","author":"Tan","year":"2016","journal-title":"Sci Rep"},{"key":"10.3233\/VES-200044_ref24","doi-asserted-by":"crossref","first-page":"1001283","DOI":"10.1371\/journal.pgen.1001283","article-title":"A meta-analysis of genome-wide association scans identifies IL18RAP, PTPN2, TAGAP, and PUS10 as shared risk loci for Crohn\u2019s disease and celiac disease,e","volume":"7","author":"Festen","year":"2017","journal-title":"PLoS Genet"},{"key":"10.3233\/VES-200044_ref25","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.jneuroim.2012.04.001","article-title":"Functional MMP-9 polymorphisms modulate plasma MMP-9 levels in multiple sclerosis patients","volume":"249","author":"Fernandes","year":"2012","journal-title":"J Neuroimmunol"},{"key":"10.3233\/VES-200044_ref26","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1002\/eji.200535628","article-title":"Human MICL (CLEC12A) is differentially glycosylated and is down-regulated following cellular activation","volume":"36","author":"Marshall","year":"2006","journal-title":"Eur J Immunol"},{"key":"10.3233\/VES-200044_ref27","doi-asserted-by":"crossref","first-page":"2707","DOI":"10.1038\/s41598-017-03027-x","article-title":"Antibody blockade of CLEC12A delays EAE onset and attenuates disease severity by impairing myeloid cell CNS infiltration and restoring positive immunity","volume":"7","author":"Sagar","year":"2017","journal-title":"Sci Rep"},{"key":"10.3233\/VES-200044_ref28","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1111\/j.1365-2362.2007.01786.x","article-title":"Glucose transporter expression on the plasma membrane of resting and activated white blood cells","volume":"37","author":"Maratou","year":"2007","journal-title":"Eur J Clin Invest"},{"key":"10.3233\/VES-200044_ref29","doi-asserted-by":"crossref","first-page":"649","DOI":"10.3390\/ijms20030649","article-title":"Interleukin-18 in Health and Disease,E","volume":"20","author":"Yasuda","year":"2019","journal-title":"Int J Mol Sci"},{"key":"10.3233\/VES-200044_ref30","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1161\/CIRCULATIONAHA.118.033942","article-title":"Platelet Serotonin Aggravates Myocardial Ischemia\/Reperfusion Injury via Neutrophil Degranulation","volume":"139","author":"Mauler","year":"2019","journal-title":"Circulation"},{"key":"10.3233\/VES-200044_ref31","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.yexmp.2015.11.011","article-title":"Neutrophil\u2019s weapons in atherosclerosis","volume":"99","author":"Chistiakov","year":"2015","journal-title":"Exp Mol Pathol"},{"key":"10.3233\/VES-200044_ref32","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1016\/j.jacc.2004.07.056","article-title":"Leukocyte count and coronary heart disease: implications for risk assessment","volume":"44","author":"Madjid","year":"2004","journal-title":"J Am Coll Cardiol"},{"key":"10.3233\/VES-200044_ref33","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.freeradbiomed.2006.11.004","article-title":"S, Coronary plaque injury triggers neutrophil activation in patients with coronary artery disease","volume":"42","author":"Rudolph","year":"2007","journal-title":"Free Radic Biol Med"},{"key":"10.3233\/VES-200044_ref34","doi-asserted-by":"crossref","first-page":"5119","DOI":"10.1111\/jcmm.14381","article-title":"Neutrophil activation in systemic capillary leak syndrome (Clarkson disease)","volume":"23","author":"Xie","year":"2019","journal-title":"J Cell Mol Med"},{"key":"10.3233\/VES-200044_ref35","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s12975-015-0431-9","article-title":"The Role of Arginase 1 in Post-Stroke Immunosuppression and Ischemic Stroke Severity","volume":"7","author":"Petrone","year":"2016","journal-title":"Transl Stroke Res"},{"key":"10.3233\/VES-200044_ref36","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1038\/sj.jcbfm.9600264","article-title":"Gene expression in blood changes rapidly in neutrophils and monocytes after ischemic stroke in humans: a microarray study","volume":"26","author":"Tang","year":"2006","journal-title":"J Cereb Blood Flow Metab"},{"key":"10.3233\/VES-200044_ref37","doi-asserted-by":"crossref","first-page":"54583","DOI":"10.18632\/oncotarget.17426","article-title":"Systematic analysis of coronary artery disease datasets revealed the potential biomarker and treatment target","volume":"8","author":"Shi","year":"2017","journal-title":"Oncotarget"},{"key":"10.3233\/VES-200044_ref38","doi-asserted-by":"crossref","first-page":"609","DOI":"10.3899\/jrheum.180455","article-title":"Gene Expression Pathways across Multiple Tissues in Antineutrophil Cytoplasmic Antibody-associated Vasculitis Reveal Core Pathways of Disease Pathology","volume":"46","author":"Friedman","year":"2019","journal-title":"J Rheumatol"},{"key":"10.3233\/VES-200044_ref39","doi-asserted-by":"crossref","first-page":"9468","DOI":"10.18632\/oncotarget.23293","article-title":"Association between matrix metalloproteinase 9 C-T polymorphism and the risk of coronary artery disease: an update systematic review and meta-analysis","volume":"9","author":"Zhang","year":"2017","journal-title":"Oncotarget"},{"key":"10.3233\/VES-200044_ref40","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s40246-016-0067-1","article-title":"Association of six CpG-SNPs in the inflammation-related genes with coronary heart disease","volume":"10(Suppl 2)","author":"Chen","year":"2016","journal-title":"Hum Genomics"},{"key":"10.3233\/VES-200044_ref41","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1161\/CIRCULATIONAHA.104.519702","article-title":"S; AtheroGene Investigators, Genetic analysis of the interleukin-18 system highlights the role of the interleukin-18 gene in cardiovascular disease","volume":"112","author":"Tiret","year":"2005","journal-title":"Circulation"},{"key":"10.3233\/VES-200044_ref42","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1111\/j.1538-7836.2012.04903.x","article-title":"Regulators of G protein signaling: role in hematopoiesis, megakaryopoiesis and platelet function","volume":"10","author":"Louwette","year":"2012","journal-title":"J Thromb Haemost"},{"key":"10.3233\/VES-200044_ref43","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1111\/jth.14382","article-title":"miR-15a-5p regulates expression of multiple proteins in the megakaryocyte GPVI signaling pathway","volume":"17","author":"Basak","year":"2019","journal-title":"J Thromb Haemost"},{"key":"10.3233\/VES-200044_ref44","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/cei.13083","article-title":"RNA-sequencing study of peripheral blood mononuclear cells in sporadic M\u00e9ni\u00e8re\u2019s disease patients: possible contribution of immunologic dysfunction to the development of this disorder","volume":"192","author":"Sun","year":"2018","journal-title":"Clin Exp Immunol"},{"key":"10.3233\/VES-200044_ref45","doi-asserted-by":"crossref","first-page":"5974","DOI":"10.1038\/s41598-018-23911-4","article-title":"Proinflammatory cytokines and response to molds in mononuclear cells of patients with Meniere disease","volume":"8","author":"Frejo","year":"2018","journal-title":"Sci Rep"},{"key":"10.3233\/VES-200044_ref46","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.3389\/fimmu.2019.01229","article-title":"Differential Proinflammatory Signature in Vestibular Migraine and Meniere Disease","volume":"10","author":"Flook","year":"2019","journal-title":"Front Immunol"}],"container-title":["Journal of Vestibular Research"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/VES-200044","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T05:24:31Z","timestamp":1777613071000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/VES-200044"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,16]]},"references-count":45,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.3233\/ves-200044","relation":{},"ISSN":["0957-4271","1878-6464"],"issn-type":[{"value":"0957-4271","type":"print"},{"value":"1878-6464","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,16]]}}}