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.
COVID-19 is generally mild in children, 1 and post-acute inflammatory conditions that are temporally associated with the virus are rare, but potentially severe. However, some children and adults experience persistent symptoms after COVID-19. 2 Long COVID has not been precisely defined, but one study reported symptoms approximately 60 days after the primary diagnosis. 3 Although adult long COVID is increasingly being studied, the magnitude of persistent symptoms in children remains unclear. This Swedish study assessed the extent, and type, of persistent symptoms in children aged 0-18 years who were admitted to one of the two paediatric hospitals in the Stockholm Region from 13 March to 31 August 2020 due to COVID-19. The inclusion criteria were the presence of a nasopharyngeal sample RT-PCR positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Children that tested positive, but were hospitalised for other reasons, were not included. Information on any persisting health issues following BRIEF REPORT
The aim of the present study was to elucidate the role of matrix metalloproteinase-9 (MMP-9), and its main inhibitor tissue inhibitor of metalloproteinases-1 (TIMP-1), in acute pyelonephritis and the process of renal scarring. Urine samples from 40 children with acute pyelonephritis, 16 children at 6-wk follow-up and 15 children with nonrenal fever were analyzed using ELISA. MMP-9 and TIMP-1 levels were compared with the outcome of pyelonephritis as measured by renal static scintigraphy. A mouse model of acute ascending pyelonephritis was used to localize the sites of production and the kinetics of MMP-9 and TIMP-1 using immunohistochemistry and ELISA. Human renal epithelial A498 cells, primary mesangial cells and monocytic THP-1 cells were stimulated by Escherichia coli. MMP-9 and TIMP-1 mRNA was analyzed by reverse transcription-PCR (RT-PCR) and protein production by ELISA. We demonstrate a significant increase of MMP-9 and TIMP-1 in the urine of children with acute pyelonephritis. Both proteins were produced mainly by leukocytes, and TIMP-1 also by resident kidney cells. Cells reacted differently after stimulation by bacteria. In mesangial cells and monocytes a decreased constitutive TIMP-1 production was found, which was in contrast to epithelial cells. Out of 40 children with pyelonephritis, 23 had higher urinary TIMP-1 than MMP-9 levels. These children had significantly more severe changes in both acute and follow-up scintigraphy scans indicating higher degree of acute tissue damage and renal scarring. Thus, our findings suggest an association between TIMP-1 and the process of renal scarring. Interstitial fibrosis is the final common end-point of progressive renal diseases. Despite its clinical significance, the mechanisms of scar formation in the kidney are still not fully understood. Generally, it is thought that the renal fibrogenesis is induced by the release of chemokines and growth factors by a number of resident cells. Their concentration gradient results in an influx of leukocytes and an increase in the number of interstitial fibroblasts. The induction phase is followed by an increased matrix production and reduced matrix degradation, which add up to a deposition of extracellular matrix (ECM) components (1). However, ECM component deposition does not seem to be the only mechanism in the pathogenesis of scarring. After direct inoculation of Escherichia coli into the kidneys of rats, contraction and collapse of the tubulointerstitial parenchyma had a greater influence than new collagen production on final fibrosis (2). In line with that, we have previously shown that mouse kidneys after experimental acute pyelonephritis were smaller compared with those from uninfected animals (3). Likewise, it seems that the end-stage kidney is rather shrunken, not enlarged or full of collagen (4).The current hypothesis suggests that the normal remodeling and healing is a result of the balance between ECM protein synthesis and degradation (5). Out of a number of matrixdegrading enzymes, gelatinases, matrix metallopro...
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