Vitamin D-Mediated Induction of Innate Immunity in Gingival Epithelial Cells
Vitamin D-Mediated Induction of Innate Immunity in Gingival Epithelial Cells
复制标题
DOI：
10.1128/iai.00099-11
复制
发表时间：
2011-06-01
影响因子：
3.1
通讯作者：
Diamond, Gill
中科院分区：
文献类型：
--
作者：
McMahon, Laura;Schwartz, Kyell;Diamond, Gill
人牙龈上皮细胞（GEC）产生肽，如β-防御素和凯萨林菌素LL-37，它们都是抗微生物的，并调节先天免疫应答。在骨髓和气道上皮细胞中，活性形式的维生素D（3）[1，25（OH）（2）D（3）]增加LL-37的表达和抗菌活性。为了检测维生素D对牙龈上皮天然免疫防御的活性，用10（-8）M 1，25（OH）（2）D（3）或乙醇处理培养的上皮细胞长达24小时。在标准单层和三维培养物中，观察到LL-37 mRNA在24 h时的时间依赖性诱导高达13倍。还观察到维生素D受体和1-α-羟化酶基因的诱导。羟化酶是功能性的，因为LL-37的诱导作用是对25（OH）D刺激的反应（3）。通过对其他先天免疫基因的微阵列分析，在用1，25（OH）（2）D处理24小时后，CD 14表达增加了4倍，髓样细胞表达的触发受体-1（TREM-1）上调了16倍（3）。TREM-1是巨噬细胞中先天免疫应答的关键放大器，导致炎症应答基因的产生增加。GEC上TREM-1的活化导致白细胞介素-8（IL-8）mRNA水平的增加。当细菌被添加到根尖表面时，用1，25（OH）（2）D（3）孵育三维培养物导致对牙周病原体伴放线菌聚集杆菌的抗菌活性增加。这项研究首次证明了维生素D对口腔上皮细胞抗菌防御的作用，表明维生素D（3）可用于增强口腔中的先天免疫防御。
Human gingival epithelial cells (GEC) produce peptides, such as beta-defensins and the cathelicidin LL-37, that are both antimicrobial and that modulate the innate immune response. In myeloid and airway epithelial cells, the active form of vitamin D(3) [1,25(OH)(2)D(3)] increases the expression and antibacterial activity of LL-37. To examine the activity of vitamin D on the innate immune defense of the gingival epithelium, cultured epithelial cells were treated with either 10(-8) M 1,25(OH)(2)D(3) or ethanol for up to 24 h. A time-dependent induction of LL-37 mRNA up to 13-fold at 24 h in both standard monolayer and three-dimensional cultures was observed. Induction of the vitamin D receptor and the 1-alpha-hydroxylase genes was also observed. The hydroxylase was functional, as LL-37 induction was observed in response to stimulation by 25(OH)D(3). Through microarray analysis of other innate immune genes, CD14 expression increased 4-fold, and triggering receptor expressed on myeloid cells-1 (TREM-1) was upregulated 16-fold after 24 h of treatment with 1,25(OH)(2)D(3). TREM-1 is a pivotal amplifier of the innate immune response in macrophages, leading to increased production by inflammatory response genes. Activation of TREM-1 on the GEC led to an increase in interleukin-8 (IL-8) mRNA levels. Incubation of three-dimensional cultures with 1,25(OH)(2)D(3) led to an increase in antibacterial activity against the periodontal pathogen Aggregatibacter actinomycetemcomitans when the bacteria were added to the apical surface. This study is the first to demonstrate the effect of vitamin D on antibacterial defense of oral epithelial cells, suggesting that vitamin D(3) could be utilized to enhance the innate immune defense in the oral cavity.