University of Oulu

Salem, A.; Almahmoudi, R.; Hagström, J.; Stark, H.; Nordström, D.; Salo, T.; Eklund, K.K. Human β-Defensin 2 Expression in Oral Epithelium: Potential Therapeutic Targets in Oral Lichen Planus. Int. J. Mol. Sci. 2019, 20, 1780.

Human β-defensin 2 expression in oral epithelium : potential therapeutic targets in oral lichen planus

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Author: Salem, Abdelhakim1,2,3; Almahmoudi, Rabeia3; Hagström, Jaana4;
Organizations: 1Department of Clinical Medicine, Clinicum, University of Helsinki, 00014 Helsinki, Finland
2Translational Immunology Research Program, University of Helsinki, 00014 Helsinki, Finland
3Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, 00014 Helsinki, Finland
4Department of Pathology, Helsinki University Hospital, Helsinki, Finland and Translational Cancer Medicine Research Program, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland
5Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
6Department of Internal Medicine, Helsinki University and Helsinki Hospital, 00014 Helsinki, Finland
7Medical Research Centre, Oulu University Hospital, 90220 Oulu, Finland
8Cancer and Translational Medicine Research Unit, University of Oulu, FI-90014 Oulu, Finland
9Department of Rheumatology, Helsinki University and Helsinki University Hospital, and Orton Orthopedic Hospital and Research Institute, 00014 Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.5 MB)
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Language: English
Published: Multidisciplinary Digital Publishing Institute, 2019
Publish Date: 2020-04-09


Human β-defensin 2 (hBD-2) is a potent antimicrobial peptide that participates in defense against invading bacteria. We recently showed that bacterial components and histamine, through histamine H4 receptor (H4R), are involved in the pathogenesis of the potentially malignant lesion, oral lichen planus (OLP). However, the underlying mechanisms remain unknown. We, therefore, investigated the role of hBD2–histamine crosstalk signaling in promoting OLP pathology. Biopsies from OLP and oral tongue squamous cell carcinoma (OTSCC) patients, and healthy controls were used. Two OTSCC cell lines and normal human oral keratinocytes (HOKs) were used. HBD-2 and other targets were mapped by immunostaining and analyzed by ImageJ2 software. The highly sensitive droplet-digital PCR technology and qRT-PCR were utilized to study the clinically derived and in vitro samples, respectively. H4R was challenged with the specific agonist HST-10 and inverse agonist ST-1007. HBD-2 was highly induced in OLP lesions. In contrast, hBD2 expression was attenuated in OTSCC tissues, while very low levels of hBD-2 messenger RNA (mRNA) were observed in OTSCC cells. Together with tumor necrosis factor-α (TNF-α), histamine upregulated hBD-2 mRNA expression in HOKs. Activation of H4R seems to modulate the expression of epithelial hBD-2. These findings suggest the involvement of hBD-2 in the pathogenesis of OLP and may, thus, be harnessed for therapeutic interventions in OLP

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Series: International journal of molecular sciences
ISSN: 1661-6596
ISSN-E: 1422-0067
ISSN-L: 1661-6596
Volume: 20
Issue: 7
Article number: 1780
DOI: 10.3390/ijms20071780
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: This research was funded by the Cancer Society of Finland (Suomen Syöpäjärjestöt), Orion Research Foundation grant, Suomen Hammaslääketieteen Säätiö (Finnish Dental Society, Apollonia), Ida Montinin Säätiö, Suomalais-Norjalainen Lääketieteen Säätiö, K. Albin Johanssons stiftelses foundation, and the Finska Läkaresällskapet.
Copyright information: © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (