Department of Clinical Medicine, Clinicum, University of Helsinki, 00014 Helsinki, Finland.
Translational Immunology Research Program, University of Helsinki, 00014 Helsinki, Finland.
Int J Mol Sci. 2019 Apr 10;20(7):1780. doi: 10.3390/ijms20071780.
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.
人 β-防御素 2 (hBD-2) 是一种有效的抗菌肽，参与防御入侵细菌。我们最近表明，细菌成分和组胺通过组胺 H4 受体 (H4R) 参与潜在恶性病变口腔扁平苔藓 (OLP) 的发病机制。然而，其潜在机制仍不清楚。因此，我们研究了 hBD2-组胺串扰信号在促进 OLP 病理中的作用。使用了来自 OLP 和口腔舌鳞状细胞癌 (OTSCC) 患者和健康对照者的活检样本。使用了两种 OTSCC 细胞系和正常的人口腔角质形成细胞 (HOK)。通过免疫染色和 ImageJ2 软件分析来绘制 HBD-2 和其他靶标。高度敏感的液滴数字 PCR 技术和 qRT-PCR 分别用于研究临床样本和体外样本。用特异性激动剂 HST-10 和反向激动剂 ST-1007 挑战 H4R。在 OLP 病变中 hBD-2 高度诱导。相比之下，在 OTSCC 组织中 hBD2 的表达减弱，而在 OTSCC 细胞中观察到非常低水平的 hBD-2 信使 RNA (mRNA)。与肿瘤坏死因子-α (TNF-α) 一起，组胺在上皮细胞 HOK 中上调 hBD-2 mRNA 表达。H4R 的激活似乎调节上皮 hBD-2 的表达。这些发现表明 hBD-2 参与了 OLP 的发病机制，因此可能被用于 OLP 的治疗干预。
