Vitamin D hormone (1,25-dihydroxyvitamin D) is involved in innate immunity and induces host defense peptides in epithelial cells, suggesting its involvement in mucosal defense against infections. Chlamydia trachomatis is a major cause of bacterial sexually transmitted disease worldwide. We tested the hypothesis that the vitamin D endocrine system would attenuate chlamydial infection. Vitamin D receptor knock-out mice (VDR(-/-)) and wild-type mice (VDR(+/+)) were infected with 10(3) inclusion forming units of Chlamydia muridarum and cervical epithelial cells (HeLa cells) were infected with C. muridarum at multiplicity of infection 5:1 in the presence and absence of 1,25-dihydroxyvitamin D3. VDR(-/-) mice exhibited significantly higher bacterial loading than wild-type VDR(+/+) mice (P<0.01) and cleared the chlamydial infection in 39 days, compared with 18 days for VDR(+/+) mice. Monocytes and neutrophils were more numerous in the uterus and oviduct of VDR(-/-) mice than in VDR(+/+) mice (P<0.05) at d 45 after infection. Pre-treatment of HeLa cells with 10nM or 100nM 1,25-dihydroxyvitamin D3 decreased the infectivity of C. muridarum (P<0.001). Several differentially expressed protein spots were detected by proteomic analysis of chlamydial-infected HeLa cells pre-treated with 1,25-dihydroxyvitamin D3. Leukocyte elastase inhibitor (LEI), an anti-inflammatory protein, was up-regulated. Expression of LEI in the ovary and oviduct of infected VDR(+/+) mice was greater than that of infected VDR(-/-) mice. We conclude that the vitamin D endocrine system reduces the risk for prolonged chlamydial infections through regulation of several proteins and that LEI is involved in its anti-inflammatory activity.

译文

维生素d激素 (1,25-二羟基维生素d) 参与先天免疫,并在上皮细胞中诱导宿主防御肽,表明其参与粘膜防御感染。沙眼衣原体是全球细菌性性传播疾病的主要原因。我们检验了维生素d内分泌系统会减轻衣原体感染的假设。维生素d受体敲除小鼠 (VDR(-/-)) 和野生型小鼠 (VDR (/)) 感染了10(3) 包涵体形成单位的衣原体和宫颈上皮细胞 (HeLa细胞) 感染多重性的C. muridarum 5:1在存在和不存在1的情况下,25-二羟基维生素d3。VDR(-/-) 小鼠表现出显著高于野生型VDR(+/+) 小鼠的细菌负荷 (P<0.01),并且在39天内清除衣原体感染,而VDR(+/+) 小鼠为18天。在感染后第45天,VDR(-/-) 小鼠的子宫和输卵管中的单核细胞和中性粒细胞多于VDR (/+) 小鼠 (P<0.05)。用10nM或100nM 1,25-二羟基维生素D3预处理HeLa细胞会降低C. muridarum的感染性 (P<0.001)。通过用1,25-二羟基维生素d3预处理的衣原体感染的HeLa细胞的蛋白质组学分析,检测了几个差异表达的蛋白质斑点。抗炎蛋白白细胞弹性蛋白酶抑制剂 (LEI) 上调。感染的VDR (/) 小鼠的卵巢和输卵管中LEI的表达大于感染的VDR(-/-) 小鼠的表达。我们得出的结论是,维生素d内分泌系统通过调节多种蛋白质降低了长期衣原体感染的风险,并且LEI参与了其抗炎活性。

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