Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3
Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3
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DOI：
10.1096/fj.04-3284com
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发表时间：
2005-07-01
期刊：
影响因子：
4.8
通讯作者：
Koeffler, HP
中科院分区：
文献类型：
--
作者：
Gombart, AF;Borregaard, N;Koeffler, HP
哺乳动物的先天免疫系统提供了一个快速的反应，以抵御包括细菌、病毒、真菌和寄生虫在内的许多感染因子的攻击。该系统的主要组成部分是阳离子抗菌肽的多种组合，包括α -防御素和β -防御素以及抗菌肽。在这项研究中，我们发现1,25-二羟基维生素D-3及其三种类似物诱导了人抗菌肽（CAMP）基因的表达。这种诱导作用在急性髓性白血病（AML）、永生化角化细胞和结肠癌细胞系以及来自两名正常人和一名AML患者的正常人骨髓（BM）来源的巨噬细胞和新鲜骨髓细胞中观察到。这种诱导是通过CAMP启动子中与维生素D受体结合的维生素D反应元件（VDRE）发生的。在小鼠细胞中未观察到CAMP的诱导，并且在小鼠vdr缺陷骨髓中CAMP mRNA的表达与野生型相似。通过对哺乳动物基因组的比较发现，灵长类动物CAMP启动子中的短分散核元件VDRE或SINE具有进化保守性，而小鼠、大鼠和犬科动物基因组中不存在这种基因。我们的研究结果揭示了1,25-二羟基维生素D3和VDR在灵长类动物先天免疫调节中的新活性。
The innate immune system of mammals provides a rapid response to repel assaults from numerous infectious agents including bacteria, viruses, fungi, and parasites. A major component of this system is a diverse combination of cationic antimicrobial peptides that include the alpha- and beta-defensins and cathelicidins. In this study, we show that 1,25-dihydroxyvitamin D-3 and three of its analogs induced expression of the human cathelicidin antimicrobial peptide (CAMP) gene. This induction was observed in acute myeloid leukemia (AML), immortalized keratinocyte, and colon cancer cell lines, as well as normal human bone marrow (BM)-derived macrophages and fresh BM cells from two normal individuals and one AML patient. The induction occurred via a consensus vitamin D response element (VDRE) in the CAMP promoter that was bound by the vitamin D receptor (VDR). Induction of CAMP in murine cells was not observed and expression of CAMP mRNA in murine VDR-deficient bone marrow was similar to wild-type levels. Comparison of mammalian genomes revealed evolutionary conservation of the VDRE in a short interspersed nuclear element or SINE in the CAMP promoter of primates that was absent in the mouse, rat, and canine genomes. Our findings reveal a novel activity of 1,25-dihydroxyvitamin D3 and the VDR in regulation of primate innate immunity.