Tada Hiroyuki, Shimizu Takamitsu, Nagaoka Isao, Takada Haruhiko
Division of Oral Microbiology, Tohoku University Graduate School of Dentistry.
Biomed Res. 2016;37(3):199-205. doi: 10.2220/biomedres.37.199.
Maxacalcitol (22-oxacalcitriol: OCT) is a synthetic vitamin D3 analog with a limited calcemic effect. In this study, we investigated whether OCT increases the production of LL-37/CAP-18, a human cathelicidin antimicrobial peptide, in human gingival/oral epithelial cells. A human gingival epithelial cell line (Ca9-22) and human oral epithelial cell lines (HSC-2, HSC-3, and HSC-4) exhibited the enhanced expression of LL-37 mRNA upon stimulation with OCT as well as active metabolites of vitamins D3 and D2. Among the human epithelial cell lines, Ca9-22 exhibited the strongest response to these vitamin D-related compounds. OCT induced the higher production of CAP-18 (ng/mL order) until 6 days time-dependently in Ca9-22 cells in culture. The periodontal pathogen Porphyromonas gingivalis was killed by treatment with the LL-37 peptide. These findings suggest that OCT induces the production of hCAP-18/LL-37 in a manner similar to that induced by the active metabolite of vitamin D3.
马沙骨化醇(22-氧杂骨化三醇:OCT)是一种合成的维生素D3类似物,其血钙升高作用有限。在本研究中,我们调查了OCT是否能增加人牙龈/口腔上皮细胞中LL-37/CAP-18(一种人组织蛋白酶抗菌肽)的产生。人牙龈上皮细胞系(Ca9-22)和人口腔上皮细胞系(HSC-2、HSC-3和HSC-4)在用OCT以及维生素D3和D2的活性代谢物刺激后,LL-37 mRNA的表达增强。在人上皮细胞系中,Ca9-22对这些维生素D相关化合物表现出最强的反应。在培养的Ca9-22细胞中,OCT在6天内呈时间依赖性地诱导产生更高水平的CAP-18(纳克/毫升级别)。用LL-37肽处理可杀死牙周病原体牙龈卟啉单胞菌。这些发现表明,OCT以类似于维生素D3活性代谢物诱导的方式诱导hCAP-18/LL-37的产生。