{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:11:27Z","timestamp":1787026287564,"version":"build-2736575974"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,11]],"date-time":"2022-05-11T00:00:00Z","timestamp":1652227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    Lymphangiogenesis and angiogenesis might have significant involvement in the pathogenesis of otitis media with effusion. This study investigated the effect of diesel exhaust particles (DEP) on inflammation and lymphangiogenesis in a mouse model of acute otitis media (AOM). BALB\/c mice were injected with LPS and exposed to 100 \u00b5g\/m\n                    <jats:sup>3<\/jats:sup>\n                    DEP. The mice were divided into four groups: control (no stimulation), AOM, AOM + DEP, and DEP + AOM.\n                  <\/jats:p>\n                  <jats:p>The effects of DEP inhalation pre- and post-DEP induction were estimated based on measurements of the auditory brainstem response, mRNA levels of lymphangiogenesis-related genes and cytokines, and histology of the middle ear. Cell viability of human middle ear epithelial cells decreased in a dose-response manner at 24 and 48 hours post-DEP exposure. DEP alone did not induce AOM. AOM-induced mice with pre- or post-DEP exposure showed thickened middle ear mucosa and increased expression of TNF-\u03b1 and IL1-\u03b2 mRNA levels compared to the control group, but increased serum IL-1\u03b2 levels were not found in the AOM + Post DEP. The mRNA expression of TLR4, VEGFA, VEGFAC, and VEGFR3 was increased by pre-AOM DEP exposure.<\/jats:p>\n                  <jats:p>The expression of VEFGA protein was stronger in the AOM + Post DEP group than in any other group. The expression of CD31 and CD45 markers in the mouse middle ear tissue was higher in the Pre DEP + AOM group than in the AOM group. This result implies that pre-exposure to DEP more strongly increases inflammation and lymphangiogenesis in a mouse model of acute otitis media.<\/jats:p>","DOI":"10.3389\/fcimb.2022.824575","type":"journal-article","created":{"date-parts":[[2022,5,11]],"date-time":"2022-05-11T02:37:27Z","timestamp":1652236647000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Effect of Angiogenesis and Lymphangiogenesis in Diesel Exhaust Particles Inhalation in Mouse Model of LPS Induced Acute Otitis Media"],"prefix":"10.3389","volume":"12","author":[{"given":"Byeong-Gon","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da Yeon","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Gyoung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An-Soo","family":"Jang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myung-Whan","family":"Suh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Ho","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Ha","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moo Kyun","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1080\/009841099157539","article-title":"Exposure to Urban Air Particulates Alters the Macrophage-Mediated Inflammatory Response to Respiratory Viral Infection","volume":"57","author":"Becker","year":"1999","journal-title":"J. Toxicol. Environ. Health A"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.1289\/ehp.9089","article-title":"Traffic-Related Air Pollution and Otitis Media","volume":"114","author":"Brauer","year":"2006","journal-title":"Environ. Health Perspect."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002336","article-title":"HIF-VEGF Pathways are Critical for Chronic Otitis Media in Junbo and Jeff Mouse Mutants","volume":"7","author":"Cheeseman","year":"2011","journal-title":"PloS Genet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1177\/000348940211100606","article-title":"Immortalization of Normal Adult Human Middle Ear Epithelial Cells Using a Retrovirus Containing the E6\/E7 Genes of Human Papillomavirus Type 16","volume":"111","author":"Chun","year":"2002","journal-title":"Ann. Otol. Rhinol. Laryngol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.envint.2018.02.019","article-title":"Effects of Exposure to Ambient Ultrafine Particles on Respiratory Health and Systemic Inflammation in Children","volume":"114","author":"Clifford","year":"2018","journal-title":"Environ. Int."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/8930904","article-title":"Otitis Media: Long-Term Effect on Central Auditory Nervous System","volume":"2019","author":"Colella-Santos","year":"2019","journal-title":"BioMed. Res. Int."},{"key":"B7","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1210\/er.2003-0027","article-title":"Vascular Endothelial Growth Factor: Basic Science and Clinical Progress","volume":"25","author":"Ferrara","year":"2004","journal-title":"Endocr. Rev."},{"key":"B8","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1038\/nature04483","article-title":"Angiogenesis as a Therapeutic Target","volume":"438","author":"Ferrara","year":"2005","journal-title":"Nature"},{"key":"B9","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1186\/s12864-018-4679-9","article-title":"Transcriptional Profiling of Human Bronchial Epithelial Cell BEAS-2B Exposed to Diesel and Biomass Ultrafine Particles","volume":"19","author":"Grilli","year":"2018","journal-title":"BMC Genomics"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2019.109837","article-title":"Panel 5: Impact of Otitis Media on Quality of Life and Development","volume":"130","author":"Hom\u00f8e","year":"2020","journal-title":"Int. J. Pediatr. Otorhinolaryngol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1080\/00016489950180450","article-title":"Expression of Vascular Endothelial Growth Factor in Otitis Media","volume":"119","author":"Jung","year":"1999","journal-title":"Acta Otolaryngol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22157868","article-title":"Toll-Like Receptors: Expression and Roles in Otitis Media","volume":"22","author":"Jung","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1165\/rcmb.2002-0115OC","article-title":"Interaction Between Respiratory Syncytial Virus and Particulate Matter in Guinea Pig Alveolar Macrophages","volume":"28","author":"Kaan","year":"2003","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1097\/ee9.0000000000000007","article-title":"Associations of Mobile Source Air Pollution During the First Year of Life With Childhood Pneumonia, Bronchiolitis, and Otitis Media","volume":"2","author":"Kennedy","year":"2018","journal-title":"Environ. Epidemiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"E39","DOI":"10.1002\/lary.24920","article-title":"Cytokine, Chemokine, and Toll-Like Receptor Expression in Middle Ear Fluids of Children with Acute Otitis Media","volume":"125","author":"Kaur","year":"2015","journal-title":"Laryngoscope"},{"key":"B16","doi-asserted-by":"publisher","first-page":"16997246","DOI":"10.1038\/s41598-021-96593-0","article-title":"Effects of Intranasal Instillation of Nanoparticulate Matter in the Olfactory Bulb","volume":"20","author":"Kim","year":"2021","journal-title":"Sci. Rep."},{"key":"B17","doi-asserted-by":"publisher","first-page":"246","DOI":"10.4168\/aair.2016.8.3.246","article-title":"Long-Term Effects of Diesel Exhaust Particles on Airway Inflammation and Remodeling in a Mouse Model","volume":"8","author":"Kim","year":"2016","journal-title":"Allergy Asthma Immunol. Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1002\/tox.22566","article-title":"Impact of Ozone on Claudins and Tight Junctions in the Lungs","volume":"33","author":"Kim","year":"2018","journal-title":"Environ. Toxicol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1183\/09031936.02.00089802","article-title":"Vascular Endothelial Growth Factor mRNA and Protein Expression in Airway Epithelial Cell Lines In Vitro","volume":"20","author":"Koyama","year":"2002","journal-title":"Eur. Respir. J."},{"key":"B20","doi-asserted-by":"publisher","first-page":"4604","DOI":"10.3390\/ijerph17124604","article-title":"Associations Between Particulate Matter and Otitis Media in Children: A Meta-Analysis","volume":"17","author":"Lee","year":"2020","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"B21","doi-asserted-by":"publisher","first-page":"110669","DOI":"10.1016\/j.ijporl.2021.110669","article-title":"The Expression of VEGF and VEGFR in Endotoxin Induced Otitis Media With Effusion in Rats","volume":"144","author":"Li","year":"2021","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"E340","DOI":"10.1002\/lary.24564","article-title":"The Role of Vascular Endothelial Growth Factor and Vascular Stability in Diseases of the Ear","volume":"124","author":"London","year":"2014","journal-title":"Laryngoscope"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036226","article-title":"Burden of Disease Caused by Otitis Media: Systematic Review and Global Estimates","volume":"7","author":"Monasta","year":"2012","journal-title":"PloS One"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1694","DOI":"10.1016\/j.jaci.2015.08.004","article-title":"Claudin 5 in a Murine Model of Allergic Asthma: Its Implication and Response to Steroid Treatment","volume":"136","author":"Moon","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.bbrc.2019.02.146","article-title":"Diesel Exhaust Particles Elevate MUC5AC and MUC5B Expression via the TLR4-Mediated Activation of ERK1\/2, P38 MAPK, and NF-\u03baB Signaling Pathways in Human Airway Epithelial Cells","volume":"512","author":"Na","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B26","doi-asserted-by":"publisher","first-page":"8792","DOI":"10.3390\/ijms21228792","article-title":"Changes in microRNA Expression in the Cochlear Nucleus and Inferior Colliculus After Acute Noise-Induced Hearing Loss","volume":"21","author":"Park","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"2193","DOI":"10.1016\/j.ijporl.2014.10.011","article-title":"Middle Ear Inflammation of Rat Induced by Urban Particles","volume":"78","author":"Park","year":"2014","journal-title":"Int. J. Pediatr. Otorhinolaryngol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"G2","DOI":"10.1016\/j.vaccine.2008.11.005","article-title":"The Burden of Otitis Media","volume":"26","author":"Rovers","year":"2008","journal-title":"Vaccine"},{"key":"B29","doi-asserted-by":"publisher","first-page":"S26","DOI":"10.1016\/s0264-410x(00)00274-7","article-title":"The Nasopharynx and the Middle Ear. Inflammatory Reactions in Middle Ear Disease","volume":"19","author":"Rynnel-Dag\u00f6\u00f6","year":"2000","journal-title":"Vaccine"},{"key":"B30","doi-asserted-by":"publisher","first-page":"3423","DOI":"10.1182\/blood-2005-04-1388","article-title":"Direct Recruitment of CRK and GRB2 to VEGFR-3 Induces Proliferation, Migration, and Survival of Endothelial Cells Through the Activation of ERK, AKT, and JNK Pathways","volume":"106","author":"Salameh","year":"2005","journal-title":"Blood"},{"key":"B31","doi-asserted-by":"publisher","first-page":"7760","DOI":"10.3390\/ijms22147760","article-title":"Regulation of VEGFR Signalling in Lymphatic Vascular Development and Disease: An Update","volume":"22","author":"Secker","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1760","DOI":"10.1016\/j.ijporl.2013.08.012","article-title":"Microarray Analysis of Gene Expression Alteration in Human Middle Ear Epithelial Cells Induced by Micro Particle","volume":"77","author":"Song","year":"2013","journal-title":"Int. J. Pediatr. Otorhinolaryngol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/j.ijporl.2011.12.003","article-title":"Effect of Diesel Exhaust Particles on Human Middle Ear Epithelial Cells","volume":"76","author":"Song","year":"2012","journal-title":"Int. J. Pediatr. Otorhinolaryngol"},{"key":"B34","article-title":"\"The Five Most Costly Children's Condition","volume-title":"Medical Expenditure Panel Survey Statistical Brief #434","author":"Soni","year":"2014"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1186\/s12889-020-09620-6","article-title":"The Impact of Hearing Impairment on Early Academic Achievement in Aboriginal Children Living in Remote Australia: A Data Linkage Study","volume":"20","author":"Su","year":"2020","journal-title":"BMC Public Health"},{"key":"B36","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1111\/micc.12132","article-title":"VEGF-C Induces Lymphangiogenesis and Angiogenesis in the Rat Mesentery Culture Model","volume":"21","author":"Sweat","year":"2014","journal-title":"Microcirculation"},{"key":"B37","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1128\/IAI.01012-09","article-title":"Enhanced Susceptibility to Acute Pneumococcal Otitis Media in Mice Deficient in Complement C1qa, Factor B, and Factor B\/C2","volume":"78","author":"Tong","year":"2010","journal-title":"Infect. Immun."},{"key":"B38","unstructured":"Air Quality Guidelines - Update 20052006"},{"key":"B39","unstructured":"WHO Global Air Quality Guidelines: Particulate Matter (PM2.5 and PM10), Ozone, Nitrogen Dioxide, Sulfur Dioxide and Carbon Monoxide2021"},{"key":"B40","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.toxlet.2009.08.006","article-title":"Diesel Exhaust Exposure Induces Angiogenesis","volume":"191","author":"Xu","year":"2009","journal-title":"Toxicol. Lett."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1769","DOI":"10.1002\/med.21496","article-title":"Potential Lymphangiogenesis Therapies: Learning From Current Antiangiogenesis Therapies-A Review","volume":"38","author":"Yamakawa","year":"2018","journal-title":"Med. Res. Rev."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1889","DOI":"10.1007\/s00405-019-05400-0","article-title":"Effect of Vascular Endothelial Growth Factor and its Receptors in Adult Otitis Media With Effusion","volume":"276","author":"Ye","year":"2019","journal-title":"Eur. Arch. Otorhinolaryngol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2020.155125","article-title":"Vascular Endothelial Growth Factor and Transforming Growth Factor \u03b2 in Hypertrophic Adenoids in Children Suffering From Otitis Media With Effusion","volume":"133","author":"Zelazowska-Rutkowska","year":"2020","journal-title":"Cytokine"},{"key":"B44","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/s0378-5955(99)00003-9","article-title":"Assessment of Hearing in 80 Inbred Strains of Mice by ABR Threshold Analyses","volume":"130","author":"Zheng","year":"1999","journal-title":"Hear Res."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2022.824575\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,11]],"date-time":"2022-05-11T02:37:33Z","timestamp":1652236653000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2022.824575\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,11]]},"references-count":44,"alternative-id":["10.3389\/fcimb.2022.824575"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2022.824575","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,11]]},"article-number":"824575"}}