Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense.
Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense.
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DOI：
10.4049/jimmunol.181.10.7090
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发表时间：
2008-11-15
期刊：
影响因子：
--
通讯作者：
Hunninghake GW
中科院分区：
文献类型：
--
作者：
Hansdottir S;Monick MM;Hinde SL;Lovan N;Look DC;Hunninghake GW
维生素D在先天免疫中的作用越来越受到重视。最近的工作已经确定了许多表达1α-羟化酶的组织，并能够激活维生素D。这种当地生产的维生素D被认为具有重要的免疫调节作用。在这篇论文中，我们发现原代肺上皮细胞表达高基线水平的活化1α-羟化酶和低水平的失活24-羟化酶。这种酶表达的结果是气道上皮细胞组成性地将无活性的25-二羟基维生素D3转化为活性的1，25-二羟基维生素D3。由肺上皮产生的活性维生素D导致具有重要先天免疫功能的维生素D调节基因的表达增加。这些包括cathelicidin抗菌肽基因和TLR共受体CD 14。双链RNA增加1α-羟化酶的表达，增加活性维生素D的产生，并与维生素D协同增加凯萨林菌素的表达。与抗微生物肽的诱导相反，维生素D减弱dsRNA诱导的NF-κB驱动的基因IL-8的表达。我们的结论是，原代上皮细胞产生活性维生素D，然后影响维生素D驱动的基因，在宿主防御中发挥重要作用的表达。此外，维生素D的存在改变了抗微生物肽和炎症细胞因子对病毒的应答。这些观察结果表明了一种新的机制，通过这种机制，非活性维生素D局部转化为活性维生素D改变了肺部的免疫功能。
The role of vitamin D in innate immunity is increasingly recognized. Recent work has identified a number of tissues that express the enzyme 1α-hydroxylase and are able to activate vitamin D. This locally produced vitamin D is believed to have important immunomodulatory effects. In this paper we show that primary lung epithelial cells express high baseline levels of activating 1α-hydroxylase and low levels of inactivating 24-hydroxylase. The result of this enzyme expression is that airway epithelial cells constitutively convert inactive 25-dihydroxyvitamin D3 to the active 1,25-dihydroxyvitamin D3. Active vitamin D that is generated by lung epithelium leads to increased expression of vitamin D regulated genes with important innate immune functions. These include the cathelicidin antimicrobial peptide gene and the TLR co-receptor CD14. Double stranded RNA increases the expression of 1α-hydroxylase, augments the production of active vitamin D, and synergizes with vitamin D to increase expression of cathelicidin. In contrast to induction of the anti-microbial peptide, vitamin D attenuates dsRNA induced expression of the NF-κB driven gene IL-8. We conclude that primary epithelial cells generate active vitamin D, which then influences the expression of vitamin D driven genes that play a major role in host defense. Furthermore the presence of vitamin D alters induction of antimicrobial peptides and inflammatory cytokines in response to viruses. These observations suggest a novel mechanism by which local conversion of inactive to active vitamin D alters immune function in the lung.
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影响因子：
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