Interleukin-2-dependent mechanisms are involved in the development of glomerulosclerosis after partial renal ablation in rats

P. Hamar, János Peti-Peterdi, Attila Szabó, Gerold Becker, Regina Flach, L. Rosivall, Uwe Heemann

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: Glomerulosclerosis is a common feature of many end-stage renal diseases. The contribution of cellular immune mechanisms has been implicated in the development of glomerulosclerosis. We investigated whether the inhibition of lymphocyte activation influences this process in an established rat model of renal hyperfiltration. Methods: After removal of two-thirds of their respective kidney mass, rats were treated with either tacrolimus (0.08 mg/kg/day) or vehicle until the end of the study (n = 10/group). The rats were pair-fed and proteinuria was assessed regularly. Twenty weeks after nephrectomy, creatinine clearance and systemic blood pressure were determined, and kidneys were harvested for morphological, immunohistological and PCR analysis. Results: In control animals, renal function started to decline from week 12, as indicated by an elevated proteinuria. Interleukin (IL)-2 and IL-2 receptor synthesis was upregulated in control animals and inhibited by tacrolimus treatment. Transforming growth factor-β (TGF-β1), platelet-derived growth factor-AA (PDGF-AA) and macrophage chemoattractant protein-1 (MCP-1) mRNA levels were upregulated in control animals, but were significantly lower in immunosuppressed hosts. Additionally, tacrolimus treatment resulted in a significant reduction of proteinuria. Morphological analysis supported these functional results; glomerular sclerosis, tubular atrophy and intimal proliferation were more pronounced in controls than in the tacrolimus group. These morphological parameters were accompanied by reduced infiltration of CD5+ (rat T-cell marker) T cells, ED1+ (rat macrophage marker) macrophages, and less intense staining for laminin and fibronectin. Conclusion: A continuous treatment with tacrolimus - an inhibitor of lymphocyte proliferation - reduced the pace of glomerulosclerosis in the remnant kidney.

Original languageEnglish
Pages (from-to)133-141
Number of pages9
JournalExperimental Nephrology
Volume9
Issue number2
Publication statusPublished - 2001

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Tacrolimus
Interleukin-2
Kidney
Proteinuria
Macrophages
Tunica Intima
T-Lymphocytes
Interleukin-2 Receptors
Platelet-Derived Growth Factor
Chemotactic Factors
Immunocompromised Host
Transforming Growth Factors
Sclerosis
Laminin
Lymphocyte Activation
Nephrectomy
Fibronectins
Chronic Kidney Failure
Atrophy
Creatinine

Keywords

  • Cytokines
  • Glomerulosclerosis
  • Growth factors
  • Hyperfiltration
  • IL-2
  • Tacrolimus

ASJC Scopus subject areas

  • Nephrology

Cite this

Interleukin-2-dependent mechanisms are involved in the development of glomerulosclerosis after partial renal ablation in rats. / Hamar, P.; Peti-Peterdi, János; Szabó, Attila; Becker, Gerold; Flach, Regina; Rosivall, L.; Heemann, Uwe.

In: Experimental Nephrology, Vol. 9, No. 2, 2001, p. 133-141.

Research output: Contribution to journalArticle

Hamar, P. ; Peti-Peterdi, János ; Szabó, Attila ; Becker, Gerold ; Flach, Regina ; Rosivall, L. ; Heemann, Uwe. / Interleukin-2-dependent mechanisms are involved in the development of glomerulosclerosis after partial renal ablation in rats. In: Experimental Nephrology. 2001 ; Vol. 9, No. 2. pp. 133-141.
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AU - Peti-Peterdi, János

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AU - Becker, Gerold

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AU - Heemann, Uwe

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N2 - Background: Glomerulosclerosis is a common feature of many end-stage renal diseases. The contribution of cellular immune mechanisms has been implicated in the development of glomerulosclerosis. We investigated whether the inhibition of lymphocyte activation influences this process in an established rat model of renal hyperfiltration. Methods: After removal of two-thirds of their respective kidney mass, rats were treated with either tacrolimus (0.08 mg/kg/day) or vehicle until the end of the study (n = 10/group). The rats were pair-fed and proteinuria was assessed regularly. Twenty weeks after nephrectomy, creatinine clearance and systemic blood pressure were determined, and kidneys were harvested for morphological, immunohistological and PCR analysis. Results: In control animals, renal function started to decline from week 12, as indicated by an elevated proteinuria. Interleukin (IL)-2 and IL-2 receptor synthesis was upregulated in control animals and inhibited by tacrolimus treatment. Transforming growth factor-β (TGF-β1), platelet-derived growth factor-AA (PDGF-AA) and macrophage chemoattractant protein-1 (MCP-1) mRNA levels were upregulated in control animals, but were significantly lower in immunosuppressed hosts. Additionally, tacrolimus treatment resulted in a significant reduction of proteinuria. Morphological analysis supported these functional results; glomerular sclerosis, tubular atrophy and intimal proliferation were more pronounced in controls than in the tacrolimus group. These morphological parameters were accompanied by reduced infiltration of CD5+ (rat T-cell marker) T cells, ED1+ (rat macrophage marker) macrophages, and less intense staining for laminin and fibronectin. Conclusion: A continuous treatment with tacrolimus - an inhibitor of lymphocyte proliferation - reduced the pace of glomerulosclerosis in the remnant kidney.

AB - Background: Glomerulosclerosis is a common feature of many end-stage renal diseases. The contribution of cellular immune mechanisms has been implicated in the development of glomerulosclerosis. We investigated whether the inhibition of lymphocyte activation influences this process in an established rat model of renal hyperfiltration. Methods: After removal of two-thirds of their respective kidney mass, rats were treated with either tacrolimus (0.08 mg/kg/day) or vehicle until the end of the study (n = 10/group). The rats were pair-fed and proteinuria was assessed regularly. Twenty weeks after nephrectomy, creatinine clearance and systemic blood pressure were determined, and kidneys were harvested for morphological, immunohistological and PCR analysis. Results: In control animals, renal function started to decline from week 12, as indicated by an elevated proteinuria. Interleukin (IL)-2 and IL-2 receptor synthesis was upregulated in control animals and inhibited by tacrolimus treatment. Transforming growth factor-β (TGF-β1), platelet-derived growth factor-AA (PDGF-AA) and macrophage chemoattractant protein-1 (MCP-1) mRNA levels were upregulated in control animals, but were significantly lower in immunosuppressed hosts. Additionally, tacrolimus treatment resulted in a significant reduction of proteinuria. Morphological analysis supported these functional results; glomerular sclerosis, tubular atrophy and intimal proliferation were more pronounced in controls than in the tacrolimus group. These morphological parameters were accompanied by reduced infiltration of CD5+ (rat T-cell marker) T cells, ED1+ (rat macrophage marker) macrophages, and less intense staining for laminin and fibronectin. Conclusion: A continuous treatment with tacrolimus - an inhibitor of lymphocyte proliferation - reduced the pace of glomerulosclerosis in the remnant kidney.

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