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

Abstract

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.

Early Diagnosis on Oral and Potentially Oral Malignant Lesions: A Systematic Review on the VELscope® Fluorescence Method

“…To overcome this problem, various diagnostic techniques have been proposed as screening tests. Among the most promising are: Exfoliative cytology (cytobrush) in its various versions [4,5], vital dyes, the use of particular light emission sources capable of visualizing areas of mucosa with anomalous characteristics through the reactions of chemoluminescence or autofluorescence [3] and, as a recent development, salivary tests and molecular markers [2,6,7,8,9,10,11,12,13,14]. Despite the continuous improvements made over time in order to eliminate the problems of sensitivity and specificity of the various methods, at present there are no certified and predictable routine methods or large-scale screening programs [15,16,17,18].…”

Tumour cells express functional lymphatic endothelium-specific hyaluronan receptor in vitro and in vivo: Lymphatic mimicry promotes oral oncogenesis?

“…The used cell lines are detailed in the supplementary materials. The ddPCR was performed as recently reported 48 . The LYVE-1 primers were designed using the Primer-BLAST tool (powered by Primer3) in NCBI website.…”

“…On the fourth day post-injection, larvae were analysed by microscopic imaging to discern fish with a tumour metastasised outside the yolk sac region. Intriguingly, the siControl group had significantly more fish with metastasis to cloaca and tail regions compared with the siLYVE-1 group, where tumour remains largely 48 . The LYVE-1 primers were designed using the Primer-BLAST tool (powered by Primer3) in NCBI website.…”

Oral lichen planus: a microbiologist point of view

“…1 ). When highly evolved eukaryotic cells, such as epithelial cells, interact with stimuli such as bacteria, viruses (such as the human herpes virus 7 or the hepatitis C virus; de Vries et al 2007 ; Ghodsi et al 2004 , respectively), fungi, or exosomal miRNAs, the cells express antibacterial peptides, such as β-defensins (potent antimicrobial peptides produced by epithelial cells; Ageitos et al 2017 ); this usually stops the infection at an early stage, protecting underlying parts of the body (Salem et al 2019 ). As it is well known, the human skin is formed by three layers; the epidermis is the first layer and constitutes a physical barrier that contains keratinized cells and specialized dendritic cells (Langerhans cells).…”