Abstract
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 D3 (25D3). 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 25D3 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.
Highlights
Urinary tract infection (UTI) remains an important disease and becomes more frequent in women after menopause
We demonstrated that the human antimicrobial peptide cathelicidin was up-regulated upon E. coli infection and that it significantly contributes to the protection of the urinary tract in humans and in mice [3]
The inactive form 25hydroxyvitamin D3 (25D3) is converted in the kidney to its active metabolite 1,25D3 by the hydroxylase CYP27B1 [6]. 1,25D3 binds to the vitamin D receptor (VDR) and is transported into the nucleus where it acts as a transcription factor
Summary
Urinary tract infection (UTI) remains an important disease and becomes more frequent in women after menopause. Due to the proximity of the highly colonized perineum, the urinary tract epithelium must be able to sense pathogens and elicit a fast innate immune response in order to keep its integrity [1,2]. We demonstrated that the human antimicrobial peptide cathelicidin was up-regulated upon E. coli infection and that it significantly contributes to the protection of the urinary tract in humans and in mice [3]. We investigate vitamin D-induced boosting of cathelicidin in the urinary bladder. Vitamin D can induce the human cathelicidin gene (CAMP) expression by binding to the vitamin D responsive element (VDRE) of the CAMP promoter [7,8] in various tissues, e.g., keratinocytes [9], respiratory epithelium [10] and monocytes [11]. Increased synthesis of cathelicidin after vitamin D treatment has been observed
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