Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases-1 in acute pyelonephritis and renal scarring

被引:47
作者
Chromek, M
Tullus, K
Hertting, O
Jaremko, G
Khalil, A
Li, YH
Brauner, A [1 ]
机构
[1] Karolinska Hosp, Microbiol & Tumorbiol Ctr, Dept Clin Microbiol, S-17176 Stockholm, Sweden
[2] Comenius Univ, Sch Med, Dept Pediat, Bratislava, Slovakia
[3] Karolinska Hosp, Astrid Lindgrens Childrens Hosp, Stockholm, Sweden
[4] Karolinska Hosp, Dept Pathol, S-10401 Stockholm, Sweden
关键词
D O I
10.1203/01.PDR.0000057575.86337.CB
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
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 (RTPCR) 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.
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页码:698 / 705
页数:8
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