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

被引:104
作者
Hertting, Olof [1 ,2 ]
Holm, Asa [1 ]
Luthje, Petra [1 ]
Brauner, Hanna
Dyrdak, Robert [1 ]
Jonasson, Aino Fianu [3 ]
Wiklund, Peter [4 ]
Chromek, Milan [1 ,2 ]
Brauner, Annelie [1 ]
机构
[1] Karolinska Inst, Div Clin Microbiol, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden
[2] Karolinska Univ Hosp, Astrid Lindgrens Childrens Hosp, Stockholm, Sweden
[3] Karolinska Inst, Dept Clin Sci, Unit Obstet & Gynecol, Stockholm, Sweden
[4] Karolinska Inst, Dept Urol, Div Surg, Stockholm, Sweden
来源
PLOS ONE | 2010年 / 5卷 / 12期
基金
瑞典研究理事会;
关键词
RESPIRATORY-TRACT INFECTION; D DEFICIENCY; 25-HYDROXYVITAMIN D-3-1-ALPHA-HYDROXYLASE; EPITHELIAL-CELLS; EXPRESSION; TUBERCULOSIS; POPULATION; RESPONSES; IMMUNITY; HEALTH;
D O I
10.1371/journal.pone.0015580
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:9
相关论文
共 36 条
[1]  
Abramoff M.D., 2004, Biophotonics International, V11, P36
[2]   Vitamin D-Directed Rheostatic Regulation of Monocyte Antibacterial Responses [J].
Adams, John S. ;
Ren, Songyang ;
Liu, Philip T. ;
Chun, Rene F. ;
Lagishetty, Venu ;
Gombart, Adrian F. ;
Borregaard, Niels ;
Modlin, Robert L. ;
Hewison, Martin .
JOURNAL OF IMMUNOLOGY, 2009, 182 (07) :4289-4295
[3]   Neisseria gonorrhoeae downregulates expression of the human antimicrobial peptide LL-37 [J].
Bergman, P ;
Johansson, L ;
Asp, V ;
Plant, L ;
Gudmundsson, GH ;
Jonsson, AB ;
Agerberth, B .
CELLULAR MICROBIOLOGY, 2005, 7 (07) :1009-1017
[4]   Expression of hTERT immortalises normal human urothelial cells without inactivation of the p16/Rb pathway [J].
Chapman, E. J. ;
Hurst, C. D. ;
Pitt, E. ;
Chambers, P. ;
Aveyard, J. S. ;
Knowles, M. A. .
ONCOGENE, 2006, 25 (36) :5037-5045
[5]   Antimicrobial mechanisms of the urinary tract [J].
Chromek, Milan ;
Brauner, Annelie .
JOURNAL OF MOLECULAR MEDICINE-JMM, 2008, 86 (01) :37-47
[6]   The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection [J].
Chromek, Milan ;
Slamova, Zuzana ;
Bergman, Peter ;
Kovacs, Laszlo ;
Podracka, L'udmila ;
Ehren, Ingrid ;
Hokfelt, Tomas ;
Gudmundsson, Gudmundur H. ;
Gallo, Richard L. ;
Agerberth, Birgitta ;
Brauner, Annelie .
NATURE MEDICINE, 2006, 12 (06) :636-641
[7]   Human bladder as a novel target for vitamin D receptor ligands [J].
Crescioli, C ;
Morelli, A ;
Adorini, L ;
Ferruzzi, P ;
Luconi, M ;
Vannelli, GB ;
Marini, M ;
Gelmini, S ;
Fibbi, B ;
Donati, S ;
Villari, D ;
Forti, G ;
Colli, E ;
Andersson, KE ;
Maggi, M .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2005, 90 (02) :962-972
[8]   Population-based epidemiologic analysis of acute pyelonephritis [J].
Czaja, Christopher A. ;
Scholes, Delia ;
Hooton, Thomas M. ;
Stamm, Walter E. .
CLINICAL INFECTIOUS DISEASES, 2007, 45 (03) :273-280
[9]   EVIDENCE OF AN AGE-RELATED DECREASE IN INTESTINAL RESPONSIVENESS TO VITAMIN-D - RELATIONSHIP BETWEEN SERUM 1,25-DIHYDROXYVITAMIN-D(3) AND INTESTINAL VITAMIN-D RECEPTOR CONCENTRATIONS IN NORMAL WOMEN [J].
EBELING, PR ;
SANDGREN, ME ;
DIMAGNO, EP ;
LANE, AW ;
DELUCA, HF ;
RIGGS, BL .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1992, 75 (01) :176-182
[10]   Vitamin D deficiency is associated with tuberculosis and latent tuberculosis infection in immigrants from Sub-Saharan Africa [J].
Gibney, Katherine B. ;
MacGregor, Lachlan ;
Leder, Karin ;
Torresi, Joseph ;
Marshall, Caroline ;
Ebeling, Peter R. ;
Biggs, Beverley-Ann .
CLINICAL INFECTIOUS DISEASES, 2008, 46 (03) :443-446