Vitamin D Induction of the Human Antimicrobial Peptide Cathelicidin in the Urinary Bladder

Vitamin D Induction of the Human Antimicrobial Peptide Cathelicidin in the Urinary Bladder
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DOI:
10.1371/journal.pone.0015580
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发表时间:
2010-12-14
期刊:
影响因子:
3.7
通讯作者:
Brauner, Annelie
Brauner, Annelie
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hertting, Olof;Holm, Asa;Brauner, Annelie

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泌尿道经常暴露于潜在的病原体,因此需要快速防御机制。 Cathelicidin 是一种人类抗菌肽,由膀胱上皮细胞表达和分泌,可保护尿路免受感染。在这里,我们证明维生素 D 可以在膀胱中诱导抗菌素。我们分析了绝经后妇女在补充 25-羟基维生素 D(3) (25D(3)) 三个月之前和之后的膀胱组织中导管素的表达情况。进行细胞培养实验以阐明导管素诱导机制。我们观察到,维生素 D 本身并没有上调本研究中女性血清或膀胱组织中的抗菌素。然而,当膀胱活检被尿路致病性大肠杆菌 (UPEC) 感染时,补充 25D(3) 后观察到导管素表达显着增加。这一观察结果在人膀胱细胞系中得到了证实,尽管在这里,抗菌素诱导的发生与感染无关。维生素 D 处理的膀胱细胞对 UPEC 的抗菌作用增强,并且与导管素的共定位表明了该肽的相关性。鉴于对常见尿路抗生素的耐药性问题日益严重,我们建议维生素 D 可能是预防尿路感染的潜在补充。
The urinary tract is frequently being exposed to potential pathogens and rapid defence mechanisms are therefore needed. Cathelicidin, a human antimicrobial peptide is expressed and secreted by bladder epithelial cells and protects the urinary tract from infection. Here we show that vitamin D can induce cathelicidin in the urinary bladder. We analyzed bladder tissue from postmenopausal women for expression of cathelicidin, before and after a three-month period of supplementation with 25-hydroxyvitamin D(3) (25D(3)). Cell culture experiments were performed to elucidate the mechanisms for cathelicidin induction. We observed that, vitamin D per se did not up-regulate cathelicidin in serum or in bladder tissue of the women in this study. However, when the bladder biopsies were infected with uropathogenic E. coli (UPEC), a significant increase in cathelicidin expression was observed after 25D(3) supplementation. This observation was confirmed in human bladder cell lines, even though here, cathelicidin induction occurred irrespectively of infection. Vitamin D treated bladder cells exerted an increased antibacterial effect against UPEC and colocalization to cathelicidin indicated the relevance of this peptide. In the light of the rapidly growing problem of resistance to common urinary tract antibiotics, we suggest that vitamin D may be a potential complement in the prevention of UTI.