Patterns of interstitial inflammation during the evolution of renal injury in experimental aristolochic acid nephropathy
BACKGROUND: Interstitial inflammation is a prominent feature associated with the severity of renal injury and progressive kidney failure. We utilized an animal model of aristolochic acid (AA)-induced nephropathy (AAN) to assess patterns of infiltration and inflammation during the evolution of tubulointerstitial damage and to relate them to the development of fibrosis.
METHODS: Male Wistar rats receiving sc daily AA or vehicle were sacrificed between Days 1 and 35. Infiltrating mononuclear cells were characterized by immunohistochemistry. The kidney infiltrating T lymphocytes were phenotyped by flow cytometry. Urinary levels of Th-1/ Th-2 cytokines, of monocyte chemoattractant protein-1 and of active transforming growth factor-beta (TGF-beta) were measured. Tissue expression of phosphorylated smad 2/3 protein was used to examine the TGF-beta signalling pathway.
RESULTS: In AA rats, monocytes/macrophages and T lymphocytes predominantly infiltrated areas of necrotic proximal tubular cells. The coexpressions of ED1 and/or Ki-67/MHCII by infiltrating cells reflected monocyte/macrophage proliferation and their activation, respectively. The accumulation of cytotoxic T lymphocytes was attested by severe signs of CD8+ cell tubulitis. The CD8/E-cadherin costaining confirmed intrarenal homing of CD8+CD103+ cells. Urinary levels of proinflammatory cytokines and of active TGF-beta significantly increased at Days 10 and 35. An early and persistent nuclear overexpression of phosphorylated smad 2/3 protein was detected in tubular and interstitial compartments.
CONCLUSION: An early and massive interstitial inflammation characterized by activated monocytes/macrophages and cytotoxic CD8+CD103+ T lymphocytes is demonstrated for the first time during the progression of experimental AAN. The involvement in an interstitial fibrosis onset of active TGF-beta is highly suggested, at least via the psmad 2/3 intracellular signalling pathway.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2008 |
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| Erschienen: |
2008 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association - 23(2008), 8 vom: 08. Aug., Seite 2480-91 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pozdzik, Agnieszka A [VerfasserIn] |
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| Links: |
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| Themen: |
94218WFP5T |
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| Anmerkungen: |
Date Completed 20.02.2009 Date Revised 24.11.2016 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1093/ndt/gfn140 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM178670227 |
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| 041 | |a eng | ||
| 100 | 1 | |a Pozdzik, Agnieszka A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Patterns of interstitial inflammation during the evolution of renal injury in experimental aristolochic acid nephropathy |
| 264 | 1 | |c 2008 | |
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| 500 | |a Date Completed 20.02.2009 | ||
| 500 | |a Date Revised 24.11.2016 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Interstitial inflammation is a prominent feature associated with the severity of renal injury and progressive kidney failure. We utilized an animal model of aristolochic acid (AA)-induced nephropathy (AAN) to assess patterns of infiltration and inflammation during the evolution of tubulointerstitial damage and to relate them to the development of fibrosis | ||
| 520 | |a METHODS: Male Wistar rats receiving sc daily AA or vehicle were sacrificed between Days 1 and 35. Infiltrating mononuclear cells were characterized by immunohistochemistry. The kidney infiltrating T lymphocytes were phenotyped by flow cytometry. Urinary levels of Th-1/ Th-2 cytokines, of monocyte chemoattractant protein-1 and of active transforming growth factor-beta (TGF-beta) were measured. Tissue expression of phosphorylated smad 2/3 protein was used to examine the TGF-beta signalling pathway | ||
| 520 | |a RESULTS: In AA rats, monocytes/macrophages and T lymphocytes predominantly infiltrated areas of necrotic proximal tubular cells. The coexpressions of ED1 and/or Ki-67/MHCII by infiltrating cells reflected monocyte/macrophage proliferation and their activation, respectively. The accumulation of cytotoxic T lymphocytes was attested by severe signs of CD8+ cell tubulitis. The CD8/E-cadherin costaining confirmed intrarenal homing of CD8+CD103+ cells. Urinary levels of proinflammatory cytokines and of active TGF-beta significantly increased at Days 10 and 35. An early and persistent nuclear overexpression of phosphorylated smad 2/3 protein was detected in tubular and interstitial compartments | ||
| 520 | |a CONCLUSION: An early and massive interstitial inflammation characterized by activated monocytes/macrophages and cytotoxic CD8+CD103+ T lymphocytes is demonstrated for the first time during the progression of experimental AAN. The involvement in an interstitial fibrosis onset of active TGF-beta is highly suggested, at least via the psmad 2/3 intracellular signalling pathway | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Aristolochic Acids |2 NLM | |
| 650 | 7 | |a SMAD2 protein, human |2 NLM | |
| 650 | 7 | |a SMAD3 protein, human |2 NLM | |
| 650 | 7 | |a Smad2 Protein |2 NLM | |
| 650 | 7 | |a Smad3 Protein |2 NLM | |
| 650 | 7 | |a Transforming Growth Factor beta |2 NLM | |
| 650 | 7 | |a aristolochic acid I |2 NLM | |
| 650 | 7 | |a 94218WFP5T |2 NLM | |
| 700 | 1 | |a Salmon, Isabelle J |e verfasserin |4 aut | |
| 700 | 1 | |a Husson, Cécile P |e verfasserin |4 aut | |
| 700 | 1 | |a Decaestecker, Christine |e verfasserin |4 aut | |
| 700 | 1 | |a Rogier, Edith |e verfasserin |4 aut | |
| 700 | 1 | |a Bourgeade, Marie-Françoise |e verfasserin |4 aut | |
| 700 | 1 | |a Deschodt-Lanckman, Monique M |e verfasserin |4 aut | |
| 700 | 1 | |a Vanherweghem, Jean-Louis |e verfasserin |4 aut | |
| 700 | 1 | |a Nortier, Joëlle L |e verfasserin |4 aut | |
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| 856 | 4 | 0 | |u http://dx.doi.org/10.1093/ndt/gfn140 |3 Volltext |
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