{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:53:24Z","timestamp":1790884404392,"version":"4.1.0"},"reference-count":32,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T00:00:00Z","timestamp":1587600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science KAKENHI grant","award":["19K09846"],"award-info":[{"award-number":["19K09846"]}]},{"name":"Health Labor Sciences Research Grant","award":["H30-Nanchitou (Nan)-Ippan-016"],"award-info":[{"award-number":["H30-Nanchitou (Nan)-Ippan-016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: The oxidative stress, induced by both environmental and intrinsic stimuli, underlies the onset and persistency of chronic rhinosinusitis (CRS). Scavenger receptors (SRs) are a broad family of transmembrane receptors involved in a dysfunctional host\u2013environment interaction through a reaction with reactive oxygen species (ROS) production. Objective: We hypothesized possible roles of two major SRs in CRS pathology that can translate to clinical phenotypes or histological subtypes: lectin-like oxidized low-density lipoproteins (LDL) receptor-1 (LOX-1) and scavenger receptor class B type 1 (SR-B1). Patients and Methods: We collected ethmoid sinus mucosa specimens and blood samples from patients with CRS with nasal polyps (CRSwNP; n = 31) or CRS without NP (CRSsNP; n = 13) and 19 control subjects. We performed an RT-PCR analysis, ELISA assay, and immunostaining to determine the expressions and distributions of LOX-1 and SR-B1. Results: The CRSwNP group showed a significant increase in LOX-1 mRNA expression compared to the control group. There was no significant difference in SR-B1 mRNA levels among the three groups. The LOX-1 mRNA levels were positively correlated with the sinus computed tomography (CT) scores. Sinus tissue, but not serum samples, showed elevated concentrations of LOX-1 protein in the CRSwNP group versus the control group. The LOX-1 protein distribution was localized in inflammatory cells and vascular endothelial cells. Conclusion: LOX-1 is a major receptor for oxidized low-density lipoprotein produced by oxidative stress. This is the first study to report alterations in LOX-1 expression and production triggered by persistent inflammatory processes in CRSwNP patients. Our findings reveal complex but important roles for SRs that may contribute to the onset of different CRS phenotypes.<\/jats:p>","DOI":"10.3390\/diagnostics10040246","type":"journal-article","created":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T10:46:22Z","timestamp":1587638782000},"page":"246","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Increased Tissue Expression of Lectin-Like Oxidized LDL Receptor-1 (LOX-1) Is Associated with Disease Severity in Chronic Rhinosinusitis with Nasal Polyps"],"prefix":"10.3390","volume":"10","author":[{"given":"Manabu","family":"Nishida","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9853-2501","authenticated-orcid":false,"given":"Sachio","family":"Takeno","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohta","family":"Takemoto","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Takahara","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9728-1264","authenticated-orcid":false,"given":"Takao","family":"Hamamoto","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Ishino","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Kawasumi","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1073\/pnas.76.1.333","article-title":"Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition","volume":"76","author":"Goldstein","year":"1979","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/ng1295-376","article-title":"Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase","volume":"11","author":"Li","year":"1995","journal-title":"Nat. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.biocel.2006.07.001","article-title":"Free radicals and antioxidants in normal physiological functions and human disease","volume":"39","author":"Valko","year":"2007","journal-title":"Int. J. Biochem. Cell Boil."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.4049\/jimmunol.1490003","article-title":"Standardizing scavenger receptor nomenclature","volume":"192","author":"Prabhudas","year":"2014","journal-title":"J. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.clim.2003.08.006","article-title":"Particulate air pollutants and asthma. A paradigm for the role of oxidative stress in PM-induced adverse health effects","volume":"109","author":"Li","year":"2003","journal-title":"Clin. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/386073a0","article-title":"An endothelial receptor for oxidized low-density lipoprotein","volume":"386","author":"Sawamura","year":"1997","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1161\/01.RES.83.3.322","article-title":"Inducible expression of lectin-like oxidized LDL receptor-1 in vascular endothelial cells","volume":"83","author":"Kume","year":"1998","journal-title":"Circ. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1172\/JCI14011","article-title":"Scavenger receptor class B type I is a multiligand HDL receptor that influences diverse physiologic systems","volume":"108","author":"Krieger","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1177\/000348949510410s02","article-title":"Quantification for staging sinusitis. The Staging and Therapy Group","volume":"167","author":"Lund","year":"1995","journal-title":"Ann. Otol. Rhinol. Laryngol. Suppl."},{"key":"ref_10","first-page":"60","article-title":"European Position Paper on Rhinosinusitis and Nasal Polyps 2012","volume":"23","author":"Fokkens","year":"2012","journal-title":"Rhinol. Suppl."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1016\/j.jaci.2018.03.004","article-title":"Endotype-driven care pathways in patients with chronic rhinosinusitis","volume":"141","author":"Bachert","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Xu, X., Ong, Y.K., and Wang, D.-Y. (2019). Novel findings in immunopathophysiology of chronic rhinosinusitis and their role in a model of precision medicine. Allergy, 14044.","DOI":"10.1111\/all.14044"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.alit.2019.07.002","article-title":"Eosinophilic chronic rhinosinusitis","volume":"68","author":"Fujieda","year":"2019","journal-title":"Allergol. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0891-5849(90)90034-G","article-title":"Reactive oxygen species and airway inflammation","volume":"9","author":"Barnes","year":"1990","journal-title":"Free Radic. Biol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1161\/CIRCRESAHA.107.149724","article-title":"Deletion of LOX-1 Reduces Atherogenesis in LDLR Knockout Mice Fed High Cholesterol Diet","volume":"100","author":"Mehta","year":"2007","journal-title":"Circ. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.accreview.2005.11.010","article-title":"Serum Soluble Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Levels Are Elevated in Acute Coronary Syndrome: A Novel Marker for Early Diagnosis","volume":"14","author":"Hayashida","year":"2005","journal-title":"ACC Curr. J. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1007\/s11745-008-3227-9","article-title":"Circulating Levels of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 are Associated with Inflammatory Markers","volume":"43","author":"Lubrano","year":"2008","journal-title":"Lipids"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.lfs.2018.02.024","article-title":"LOX-1 receptor: A potential link in atherosclerosis and cancer","volume":"198","author":"Balzan","year":"2018","journal-title":"Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.mvr.2016.02.006","article-title":"Roles of LOX-1 in microvascular dysfunction","volume":"105","author":"Lubrano","year":"2016","journal-title":"Microvasc. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.4049\/jimmunol.1501709","article-title":"Human SR-BI and SR-BII Potentiate Lipopolysaccharide-Induced Inflammation and Acute Liver and Kidney Injury in Mice","volume":"196","author":"Baranova","year":"2016","journal-title":"J. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"19826","DOI":"10.1074\/jbc.M109.020933","article-title":"Scavenger Receptor BI Protects against Septic Death through Its Role in Modulating Inflammatory Response","volume":"284","author":"Guo","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1038\/nature06905","article-title":"NF-\u03baB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1\u03b1","volume":"453","author":"Rius","year":"2008","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e23","DOI":"10.2500\/ajra.2011.25.3563","article-title":"Increased Expression of Angiogenin in Nasal Polyps","volume":"25","author":"Hwang","year":"2011","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1007\/s00405-002-0467-9","article-title":"Immunohistochemical expression of VEGF and VEGF receptors in nasal polyps as compared to normal turbinate mucosa","volume":"259","author":"Wittekindt","year":"2002","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1177\/194589240501900102","article-title":"Expression, localization, and significance of vascular permeability\/vascular endothelial growth factor in nasal polyps","volume":"19","author":"Gosepath","year":"2005","journal-title":"Am. J. Rhinol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1373\/clinchem.2009.140707","article-title":"LOX Index, a Novel Predictive Biochemical Marker for Coronary Heart Disease and Stroke","volume":"56","author":"Inoue","year":"2010","journal-title":"Clin. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1378\/chest.11-0302","article-title":"Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Modulates Endothelial Apoptosis in Obstructive Sleep Apnea","volume":"140","author":"Akinnusi","year":"2011","journal-title":"Chest"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.jpeds.2018.10.036","article-title":"A Pilot Study of Soluble Form of LOX-1 as a Novel Biomarker for Neonatal Hypoxic-Ischemic Encephalopathy","volume":"206","author":"Akamatsu","year":"2019","journal-title":"J. Pediatr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1136\/thx.54.10.947","article-title":"Nasal nitric oxide in man","volume":"54","author":"Lundberg","year":"1999","journal-title":"Thorax"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/s00011-006-6111-1","article-title":"Nitric oxide in upper airways inflammatory diseases","volume":"56","author":"Maniscalco","year":"2007","journal-title":"Inflamm. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1378\/chest.09-2090","article-title":"Exhaled Nitric Oxide in Pulmonary Diseases","volume":"138","author":"Barnes","year":"2010","journal-title":"Chest"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.anl.2013.02.001","article-title":"Increased exhaled nitric oxide and its oxidation metabolism in eosinophilic chronic rhinosinusitis","volume":"40","author":"Takeno","year":"2013","journal-title":"Auris Nasus Larynx"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/10\/4\/246\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:09:07Z","timestamp":1760364547000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/10\/4\/246"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,23]]},"references-count":32,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["diagnostics10040246"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics10040246","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,23]]}}}