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.

• Authors: Abdelhakim Salem, Rabeia Almahmoudi, Jaana Hagström, Holger Stark, Dan Nordström, Tuula Salo, Kari K Eklund
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 20 Issue 7 (Apr 10 2019) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 30974892 (Publication Type: Journal Article)

Chemical References

• DEFB4A protein, human
• Tumor Necrosis Factor-alpha
• beta-Defensins
• Histamine

Topics

• Cell Line, Tumor
• Female
• Histamine (metabolism)
• Humans
• Keratinocytes (metabolism, pathology)
• Lichen Planus, Oral (metabolism, pathology)
• Male
• Signal Transduction
• Tumor Necrosis Factor-alpha (metabolism)
• Up-Regulation
• beta-Defensins (biosynthesis)