Korean Journal of Nephrology 2009;28(4):326-334.
The Role of MCP 1 and IL 6 on the Progress of Crescentic Glomerulonephritis
Hyewon Hahn, M.D.1, Eun Young Um, B.A.2 and Il Soo Ha, M.D.3
Department of Pediatrics, Eulji University School of Medicine1 Seoul National University Hospital Clinical Research Institute2 Seoul National University College of Medicine3
기초연구 : The Role of MCP 1 and IL 6 on the Progress of Crescentic Glomerulonephritis
Hyewon Hahn, M.D.1, Eun Young Um, B.A.2 and Il Soo Ha, M.D.3
Department of Pediatrics, Eulji University School of Medicine1 Seoul National University Hospital Clinical Research Institute2 Seoul National University College of Medicine3
Abstract
Purpose:Growing data on the relationship between cytokine expression and the progression of renal diseases make these cytokines potential targets for therapeutic interventions. Weexamined the helper T1-cell- and macrophage-associated cytokines in anti-glomerular basement membrane (GBM) antibody-induced nephritis in mice and their temporal relationships with renal tissue fibrosis. Methods:Kidneys were harvested on days 1, 3, 7, 11, and 16 after glomerulonephritis was induced with anti-GBM antibody. The progression of renal fibrosis was serially monitored to quantitate the accumulation of cortical extracellular matrix, and various cytokines were measured simultaneously. Results:A single injection of anti-GBM antibody successfully produced severe crescentic glomerulonephritis. Proteinuria increased abruptly and both mesangial matrix expansion and interstitial fibrosis progressed rapidly. Cortical fibronectin and type III collagen increased continuously, reaching a peak on day 7, and the deposition of type III collagen followed the same pattern, in parallel with that of urinary transforming growth factor 1 (TGF-1) expression. Serial cytokine measurements revealed a sustained increase in interleukin (IL) 6 and monocyte chemoattractant protein 1 (MCP1) from day 3, but neither IL12, IL18, nor interferon changed significantly. Real-time polymerase chain reaction confirmed these features at the transcription level. Conclusion:MCP1 and IL6 correlated with the progression of renal fibrosis, with no increase in Th1- inducing cytokines. This confirms MCP1 and IL6 as attractive therapeutic targets for renal fibrosis in crescentic glomerulonephritis.
Key Words: Anti-glomerular basement membrane disease, Fibrosis, Interleukin-6, Monocyte chemoattractant protein
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