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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收藏
页码:698 / 705
页数:8
相关论文
共 42 条
  • [11] Changes in matrix metalloproteinases during the evolution of interstitial renal fibrosis in a rat experimental model
    Gonzalez-Avila, G
    Iturria, C
    Vadillo-Ortega, F
    Ovalle, C
    Montano, M
    [J]. PATHOBIOLOGY, 1998, 66 (05) : 196 - 204
  • [12] Interleukin-8 receptor knockout mice have subepithelial neutrophil entrapment and renal scarring following acute pyelonephritis
    Hang, L
    Frendéus, B
    Godaly, G
    Svanborg, C
    [J]. JOURNAL OF INFECTIOUS DISEASES, 2000, 182 (06) : 1738 - 1748
  • [13] Hang L, 1999, J IMMUNOL, V162, P3037
  • [14] Immunoregulatory cytokines modify Escherichia coli induced uroepithelial cell IL-6 and IL-8 responses
    Hedges, SR
    Bjarnadottir, M
    Agace, W
    Hang, L
    Svanborg, C
    [J]. CYTOKINE, 1996, 8 (09) : 686 - 697
  • [15] Hewitson TD, 1998, J AM SOC NEPHROL, V9, P632
  • [16] Expression of matrix metalloproteinases (MMP-2 and -9) and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in acute myelogenous leukaemia blasts: comparison with normal bone marrow cells
    Janowska-Wieczorek, A
    Marquez, LA
    Matsuzaki, A
    Hashmi, HR
    Larratt, LM
    Boshkov, LM
    Turner, AR
    Zhang, MC
    Edwards, DR
    [J]. BRITISH JOURNAL OF HAEMATOLOGY, 1999, 105 (02) : 402 - 411
  • [17] John Anitha, 2001, Pathology and Oncology Research, V7, P14
  • [18] Paracrine stimulation of human renal fibroblasts by proximal tubule cells
    Johnson, DW
    Saunders, HJ
    Baxter, RC
    Field, MJ
    Pollock, CA
    [J]. KIDNEY INTERNATIONAL, 1998, 54 (03) : 747 - 757
  • [19] Kernacki KA, 1999, INVEST OPHTH VIS SCI, V40, P3168
  • [20] Angiotensin II type 1 receptor antagonist (losartan) down-regulates transforming growth factor-β in experimental acute pyelonephritis
    Khalil, A
    Tullus, K
    Bakhiet, M
    Burman, LG
    Jaremko, G
    Brauner, A
    [J]. JOURNAL OF UROLOGY, 2000, 164 (01) : 186 - 191