title: Vitamin D induction of the human antimicrobial Peptide cathelicidin in the urinary bladder.
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.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Division of Clinical Microbiology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Hertting
authors.forename: Åsa
authors.initials: Å
authors.lastname: Holm
authors.forename: Petra
authors.initials: P
authors.lastname: Lüthje
authors.forename: Hanna
authors.initials: H
authors.lastname: Brauner
authors.forename: Robert
authors.initials: R
authors.lastname: Dyrdak
authors.forename: Aino Fianu
authors.initials: AF
authors.lastname: Jonasson
authors.forename: Peter
authors.initials: P
authors.lastname: Wiklund
authors.forename: Milan
authors.initials: M
authors.lastname: Chromek
authors.forename: Annelie
authors.initials: A
authors.lastname: Brauner
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000096:biosynthesis; D000368:Aged; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002112:Calcifediol / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D001743:Urinary Bladder / Q000378:metabolism* / Q000382:microbiology; D014551:Urinary Tract / Q000473:pathology; D014552:Urinary Tract Infections / Q000378:metabolism / Q000517:prevention & control*; D056689:Uropathogenic Escherichia coli / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism*; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D014807:Vitamin D; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002112:Calcifediol; D054804:Cathelicidins