Regulation of the human cathelicidin antimicrobial peptide gene by 1α,25-dihydroxyvitamin D3 in primary immune cells.
Regulation of the human cathelicidin antimicrobial peptide gene by 1α,25-dihydroxyvitamin D3 in primary immune cells.
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DOI：
10.1016/j.jsbmb.2014.02.004
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发表时间：
2014-09
影响因子：
4.1
通讯作者：
Gombart, Adrian F.
中科院分区：
文献类型：
--
作者：
Lowry, Malcolm B.;Guo, Chunxiao;Borregaard, Niels;Gombart, Adrian F.
人类抗菌素抗菌肽基因(hCAP18/LL-37)的产生受1α，25-二羟基维生素D3(1，25D3)的调节，在先天性免疫细胞杀死病原体中起关键作用。此外，分泌的IL-37结合细胞外受体，调节先天免疫细胞和获得性免疫细胞的招募和活性。有证据表明，在感染期间，局部激活的免疫细胞产生更多的1，25D3，从而增加hCAP18/LL-37的产生。HCAP18/LL-37在不同免疫细胞类型之间的相对表达水平尚未得到很好的描述。本研究的目的是确定人外周血免疫细胞中hCAP18/LL-37的相对水平，并确定1，25D3在多大程度上增加其在外周血源性细胞中的表达。我们首次展示了hCAP18在新分离的细胞中的表达层次，其中淋巴细胞中水平较低，单核细胞中水平中等，中性粒细胞中水平最高。在外周血源性细胞中，1，25D3处理后hCAP18在巨噬细胞中的表达水平最高，而GM-CSF来源的树突状细胞和破骨细胞中的hCAP18水平相对较低。我们还测试了甲状旁腺激素与1，25D3联合治疗是否会像已报道的那样在皮肤细胞中增强hCAP18的诱导，但我们没有在任何被测试的免疫细胞中发现增强作用。我们的结果表明，hCAP18在不同的细胞类型和谱系中的表达水平不同。此外，1，25D3对巨噬细胞和树突状细胞中hCAP18的有效诱导可能调节感染部位的天然免疫细胞和获得性免疫细胞的功能。
Production of the human cathelicidin antimicrobial peptide gene (hCAP18/LL-37), is regulated by 1α,25-dihydroxyvitamin D3 (1,25D3) and is critical in the killing of pathogens by innate immune cells. In addition, secreted LL-37 binds extracellular receptors and modulates the recruitment and activity of both innate and adaptive immune cells. Evidence suggests that during infections activated immune cells locally produce increased levels of 1,25D3 thus increasing production of hCAP18/LL-37. The relative expression levels of hCAP18/LL-37 among different immune cell types are not well characterized. The aim of this study was to determine the relative levels of hCAP18/LL-37 in human peripheral blood immune cells and determine to what extent 1,25D3 increased its expression in peripheral blood-derived cells. We show for the first time, a hierarchy of expression of hCAP18 in freshly isolated cells with low levels in lymphocytes, intermediate levels in monocytes and the highest levels found in neutrophils. In peripheral blood-derived cells, the highest levels of hCAP18 following treatment with 1,25D3 were in macrophages, while comparatively lower levels were found in GM-CSF-derived dendritic cells and osteoclasts. We also tested whether treatment with parathyroid hormone in combination with 1,25D3 would enhance hCAP18 induction as has been reported in skin cells, but we did not find enhancement in any immune cells tested. Our results indicate that hCAP18 is expressed at different levels according to cell type and lineage. Furthermore, potent induction of hCAP18 by 1,25D3 in macrophages and dendritic cells may modulate functions of both innate and adaptive immune cells at sites of infection.
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影响因子：
3.1
作者：
Gombart AF
通讯作者：
Gombart AF
影响因子：
4.8
作者：
Gombart, AF;Borregaard, N;Koeffler, HP
通讯作者：
Koeffler, HP
影响因子：
56.9
作者：
Liu, PT;Stenger, S;Modlin, RL
通讯作者：
Modlin, RL
影响因子：
82.9
作者：
Chromek, Milan;Slamova, Zuzana;Brauner, Annelie
通讯作者：
Brauner, Annelie
DOI：
10.1016/j.ecl.2010.02.010
发表时间：
2010-06
影响因子：
4.5
作者：
Hewison, Martin
通讯作者：
Hewison, Martin