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Human β-Defensin 2 Expression in Oral Epithelium: Potential Therapeutic Targets in Oral Lichen Planus

1
Department of Clinical Medicine, Clinicum, University of Helsinki, 00014 Helsinki, Finland
2
Translational Immunology Research Program, University of Helsinki, 00014 Helsinki, Finland
3
Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, 00014 Helsinki, Finland
4
Department of Pathology, Helsinki University Hospital, Helsinki, Finland and Translational Cancer Medicine Research Program, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland
5
Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
6
Department of Internal Medicine, Helsinki University and Helsinki Hospital, 00014 Helsinki, Finland
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Medical Research Centre, Oulu University Hospital, 90220 Oulu, Finland
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Cancer and Translational Medicine Research Unit, University of Oulu, FI-90014 Oulu, Finland
9
Department of Rheumatology, Helsinki University and Helsinki University Hospital, and Orton Orthopedic Hospital and Research Institute, 00014 Helsinki, Finland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(7), 1780; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20071780
Received: 26 February 2019 / Revised: 2 April 2019 / Accepted: 9 April 2019 / Published: 10 April 2019
(This article belongs to the Section Biochemistry)
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. View Full-Text
Keywords: histamine; histamine H4 receptor; human beta defensin 2; mast cells; inflammation; bacterial lipopolysaccharide (LPS); OPMDs; oral epithelium; oral cancer; oral tongue squamous cell carcinoma histamine; histamine H4 receptor; human beta defensin 2; mast cells; inflammation; bacterial lipopolysaccharide (LPS); OPMDs; oral epithelium; oral cancer; oral tongue squamous cell carcinoma
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MDPI and ACS Style

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. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20071780

AMA Style

Salem A, Almahmoudi R, Hagström J, Stark H, Nordström D, Salo T, Eklund KK. Human β-Defensin 2 Expression in Oral Epithelium: Potential Therapeutic Targets in Oral Lichen Planus. International Journal of Molecular Sciences. 2019; 20(7):1780. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20071780

Chicago/Turabian Style

Salem, Abdelhakim, Rabeia Almahmoudi, Jaana Hagström, Holger Stark, Dan Nordström, Tuula Salo, and Kari K. Eklund 2019. "Human β-Defensin 2 Expression in Oral Epithelium: Potential Therapeutic Targets in Oral Lichen Planus" International Journal of Molecular Sciences 20, no. 7: 1780. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20071780

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