{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:27:39Z","timestamp":1772252859653,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T00:00:00Z","timestamp":1639094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Smoking, laryngopharyngeal reflux, and vocal fold abuse can promote the development of Reinke\u2019s oedema, leading to vocal fold dysfunction and injury. The aim of the work was to investigate the appearance and distribution of proliferation marker Ki-67 (Ki-67), interleukin 10 (IL-10), interleukin 1 alpha (IL-1\u03b1), and protein gene peptide 9.5 (PGP 9.5) in Reinke\u2019s oedema-affected larynx tissue. Methods: A routine histological and immunohistochemical Reinke\u2019s oedema and control group patient analysis was conducted. We used the biotin\u2013streptavidin biochemical method to detect Ki-67, IL-10, IL-1\u03b1, and PGP 9.5 The semiquantitative grading method was used to evaluate immunoreactive cells\u2019 appearance and local distribution. A Mann\u2013Whitney U test and Spearman\u2019s rank coefficient were performed. Results: A low positive correlation between IL-1\u03b1 epithelial and subepithelial immunoreactive cells in the patient group was found. Mann\u2013Whitney U tests revealed significant patient and control group immunoreactive marker differences. All examined markers showed a higher number of immunoreactive structures in the patient group. Conclusions: Intensive proliferation of the surface epithelium was observed in patient tissues. The notable increase in IL-10 positive structures indicates the dominant anti-inflammatory tissue response. An increased number of IL-1\u03b1 structures in the larynx epithelium and subepithelium in the patient group is linked to inflammation, proliferation, and tissue remodelling. The PGP 9.5 expression increase is involved in the morphopathogenesis of Reinke\u2019s oedema.<\/jats:p>","DOI":"10.3390\/life11121379","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T01:29:33Z","timestamp":1639358973000},"page":"1379","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Distribution and Appearance of Ki-67, IL-1\u03b1, IL-10, and PGP 9.5 in Reinke\u2019s Oedema-Affected Larynx Tissue Compared with Control Tissue"],"prefix":"10.3390","volume":"11","author":[{"given":"Vita","family":"Konopecka","sequence":"first","affiliation":[{"name":"Institute of Anatomy and Anthropology, Riga Stradins University, LV-1007 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9804-4666","authenticated-orcid":false,"given":"Mara","family":"Pilmane","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Anthropology, Riga Stradins University, LV-1007 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dins","family":"Sumerags","sequence":"additional","affiliation":[{"name":"Cesu Clinic, LV-1010 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunta","family":"Sumeraga","sequence":"additional","affiliation":[{"name":"Pauls Stradins Clinical University Hospital, LV-1002 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.otc.2019.03.006","article-title":"Reinke\u2019s Edema","volume":"52","author":"Tavaluc","year":"2019","journal-title":"Otolaryngol. Clin. North. Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.1002\/lary.25424","article-title":"Evaluation of the Prevalence of and Factors Associated with Laryngeal Diseases among the General Population: Prevalence of Laryngeal Diseases","volume":"125","author":"Hah","year":"2015","journal-title":"Laryngoscope"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"194","DOI":"10.14639\/0392-100X-1544","article-title":"Efficacy of Microsurgery in Reinke\u2019s Oedema Evaluated by Traditional Voice Assessment Integrated with the Vocal Extent Measure (VEM)","volume":"38","author":"Salmen","year":"2018","journal-title":"Acta Otorhinolaryngol. Ital."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1080\/00016480410017279","article-title":"Extracellular Matrix of Reinke\u2019s Space in Some Pathological Conditions","volume":"124","author":"Klapan","year":"2004","journal-title":"Acta Oto-Laryngol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1080\/00016480310001321","article-title":"Steroid Injection for Reinke\u2019s Edema Using Fiberoptic Laryngeal Surgery","volume":"123","author":"Tateya","year":"2003","journal-title":"Acta Oto-Laryngol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1053\/ajot.2002.30961","article-title":"Reinke\u2019s Edema and Risk Factors: Clinical and Histopathologic Aspects","volume":"23","author":"Marcotullio","year":"2002","journal-title":"Am. J. Otolaryngol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.otohns.2009.05.033","article-title":"The Significance of Laryngopharyngeal Reflux in Benign Vocal Mucosal Lesions","volume":"141","author":"Chung","year":"2009","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1177\/000348949710600701","article-title":"Reinke\u2019s Edema: Phonatory Mechanisms and Management Strategies","volume":"106","author":"Zeitels","year":"1997","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1007\/s00508-010-1349-6","article-title":"The Role of Allergy in the Etiology of Reinke\u2019s Edema on Vocal Folds","volume":"122","author":"Kravos","year":"2010","journal-title":"Wien. Klin. Wochenschr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/lary.24911","article-title":"Gender and Age in Benign Vocal Fold Lesions: Benign VF Lesions: Gender and Age","volume":"125","author":"Zhukhovitskaya","year":"2015","journal-title":"Laryngoscope"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1177\/000348949910801108","article-title":"Electron Microscopic and Immunohistochemical Investigation of Reinke\u2019s Edema","volume":"108","author":"Sato","year":"1999","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_12","first-page":"61","article-title":"Histological and Electron Microscopic Investigation of Reinke\u2019s Edema","volume":"54","author":"Pastuszek","year":"2003","journal-title":"Pol. J. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/ijc.2910310104","article-title":"Production of a Mouse Monoclonal Antibody Reactive with a Human Nuclear Antigen Associated with Cell Proliferation","volume":"31","author":"Gerdes","year":"1983","journal-title":"Int. J. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1002\/path.1016","article-title":"The Ki-67 Protein Interacts with Members of the Heterochromatin Protein 1 (HP1) Family: A Potential Role in the Regulation of Higher-Order Chromatin Structure","volume":"196","author":"Scholzen","year":"2002","journal-title":"J. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9","article-title":"The Ki-67 Protein: From the Known and the Unknown","volume":"182","author":"Scholzen","year":"2000","journal-title":"J. Cell. Phys."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"814.e1","DOI":"10.1016\/j.jvoice.2012.03.008","article-title":"Vocal Exercise May Attenuate Acute Vocal Fold Inflammation","volume":"26","author":"Li","year":"2012","journal-title":"J. Voice"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/nri2097","article-title":"TH1 Cells Control Themselves by Producing Interleukin-10","volume":"7","author":"Vieira","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1615\/CritRevImmunol.v32.i1.30","article-title":"Role of Interleukin 10 Transcriptional Regulation in Inflammation and Autoimmune Disease","volume":"32","author":"Iyer","year":"2012","journal-title":"Crit. Rev. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"R126","DOI":"10.1186\/ar3064","article-title":"Exercise Increases Interleukin-10 Levels Both Intraarticularly and Peri-Synovially in Patients with Knee Osteoarthritis: A Randomized Controlled Trial","volume":"12","author":"Helmark","year":"2010","journal-title":"Arthritis Res. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4835","DOI":"10.4049\/jimmunol.1102048","article-title":"IL-1\u03b1 and IL-1\u03b2 Recruit Different Myeloid Cells and Promote Different Stages of Sterile Inflammation","volume":"187","author":"Rider","year":"2011","journal-title":"J. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"15942","DOI":"10.1074\/jbc.M114.557561","article-title":"Release of Interleukin-1\u03b1 or Interleukin-1\u03b2 Depends on Mechanism of Cell Death","volume":"289","author":"England","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3720","DOI":"10.1182\/blood-2010-07-273417","article-title":"Interleukin-1 in the Pathogenesis and Treatment of Inflammatory Diseases","volume":"117","author":"Dinarello","year":"2011","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.smim.2018.10.006","article-title":"Interleukin-1\u03b1 as an Intracellular Alarmin in Cancer Biology","volume":"38","author":"Voronov","year":"2018","journal-title":"Semin. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1038\/nm0707-778","article-title":"IL-1\u03b1 Responds to Necrotic Cell Death","volume":"13","author":"Elkon","year":"2007","journal-title":"Nat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1111\/j.1365-2141.2004.05205.x","article-title":"Expression of Protein Gene Product 9\u00b75 (PGP9\u00b75)\/Ubiquitin-C-Terminal Hydrolase 1 (UCHL-1) in Human Myeloma Cells: Expression of PGP9\u00b75 in Myeloma","volume":"127","author":"Otsuki","year":"2004","journal-title":"Br. J. Haematol."},{"key":"ref_26","first-page":"102","article-title":"Assesment of Protein Gene Product (Pgp9.5) Enzyme Activity against Potential Peptide Substrate","volume":"41","author":"Pirim","year":"2009","journal-title":"Eurasian J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1097\/00000478-199911000-00011","article-title":"PGP9.5: A Marker for Cellular Neurothekeoma","volume":"23","author":"Wang","year":"1999","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1136\/thx.50.5.551","article-title":"Changes in Neuroendocrine Elements in Bronchial Mucosa in Chronic Lung Disease in Adults","volume":"50","author":"Pilmane","year":"1995","journal-title":"Thorax"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Vitenberga, Z., Pilmane, M., and Babjoni\u0161eva, A. (2019). An Insight into COPD Morphopathogenesis: Chronic Inflammation, Remodelling, and Antimicrobial Defense. Medicina, 55.","DOI":"10.3390\/medicina55080496"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"389","DOI":"10.12697\/poa.2011.20.36","article-title":"Distribution of Neuropeptides in Nasal and Nasopharyngeal Mucosa in Patients with the Post Nasal Drip Syndrome","volume":"20","author":"Sumeraga","year":"2012","journal-title":"Pap. Anthropol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Goida, J., and Pilmane, M. (2021). Characterization of Macrophages and TNF-\u03b1 in Cleft Affected Lip Tissue. Cosmetics, 8.","DOI":"10.3390\/cosmetics8020042"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1214\/aoms\/1177730491","article-title":"On a Test of Whether One of Two Random Variables Is Stochastically Larger than the Other","volume":"18","author":"Mann","year":"1947","journal-title":"Ann. Math. Statist."},{"key":"ref_33","first-page":"69","article-title":"Statistics Corner: A Guide to Appropriate Use of Correlation Coefficient in Medical Research","volume":"24","author":"Mukaka","year":"2012","journal-title":"Malawi Med. J."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Pilmane, M., Sidhoma, E., Akota, I., and Kazoka, D. (2019). Characterization of Cytokines and Proliferation Marker Ki67 in Cleft Affected Lip Tissue. Medicina, 55.","DOI":"10.3390\/medicina55090518"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1038\/ni.3503","article-title":"Interleukin 1\u03b1 and the Inflammatory Process","volume":"17","author":"Shayakhmetov","year":"2016","journal-title":"Nat. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.otohns.2010.04.264","article-title":"Effects of Raised-Intensity Phonation on Inflammatory Mediator Gene Expression in Normal Rabbit Vocal Fold","volume":"143","author":"Swanson","year":"2010","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.molcel.2011.07.037","article-title":"Granzyme B-Dependent Proteolysis Acts as a Switch to Enhance the Proinflammatory Activity of IL-1\u03b1","volume":"44","author":"Afonina","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1038\/nm1603","article-title":"Identification of a Key Pathway Required for the Sterile Inflammatory Response Triggered by Dying Cells","volume":"13","author":"Chen","year":"2007","journal-title":"Nat. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1126\/science.aad7969","article-title":"Pulmonary Neuroendocrine Cells Function as Airway Sensors to Control Lung Immune Response","volume":"351","author":"Branchfield","year":"2016","journal-title":"Science"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/11\/12\/1379\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:45:10Z","timestamp":1760168710000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/11\/12\/1379"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,10]]},"references-count":39,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["life11121379"],"URL":"https:\/\/doi.org\/10.3390\/life11121379","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-50922\/v1","asserted-by":"object"}]},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,10]]}}}