State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, 14 3rd Section S Renmin Road, Chengdu 610041, China.
Cell Immunol. 2013 May-Jun;283(1-2):45-50. doi: 10.1016/j.cellimm.2013.06.007. Epub 2013 Jun 19.
Vitamin D and its metabolites have been recognized as key determinants in innate immune modulation. In this study, we investigated the regulation of antibacterial functions of oral keratinocyte cells by 25-hydroxyvitamin D3 (25VD3). OKF6/TERT2 cells, an immortalized human oral keratinocyte cell line, were transfected with or without 24-hydroxylase small interfering RNA (siRNA) and incubated with different amounts of 25VD3. These epithelial cells expressed high levels of inactivating 24-hydroxylase (CYP24A1) and relatively low levels of activating 1α-hydroxylase (CYP27B1) in the presence of 25VD3. 25VD3 influenced the expression of vitamin D-driven genes and cathelicidin in a dose-related manner. SiRNA specific to 24-hydroxylase augmented the cathelicidin production and subseqently influenced the antibacterial activity on multispecies of oral pathogens. These observations suggest that 25VD3 is capable of stimulating cathelicidin production and modulating antibacterial function upon CYP24A1 knochdown in oral epithelial cells, and indicate novel mechanisms that 25VD3 may enhance antibacterial ability in oral keratinocytes.
维生素 D 及其代谢物已被认为是先天免疫调节的关键决定因素。在这项研究中,我们研究了 25-羟维生素 D3(25VD3)对口腔角质形成细胞抗菌功能的调节。OKF6/TERT2 细胞是一种永生化的人口腔角质形成细胞系,用或不用 24-羟化酶小干扰 RNA(siRNA)转染,并与不同剂量的 25VD3 孵育。这些上皮细胞在 25VD3 的存在下表达高水平的失活 24-羟化酶(CYP24A1)和相对低水平的激活 1α-羟化酶(CYP27B1)。25VD3 以剂量相关的方式影响维生素 D 驱动基因和抗菌肽的表达。针对 24-羟化酶的特异性 siRNA 增强了抗菌肽的产生,并随后影响了对多种口腔病原体的抗菌活性。这些观察结果表明,25VD3 能够刺激口腔上皮细胞中 CYP24A1 敲低后的抗菌肽产生和调节抗菌功能,并表明 25VD3 可能增强口腔角质形成细胞抗菌能力的新机制。