The Role of MCP 1 and IL 6 on the Progress of Crescentic Glomerulonephritis / 대한신장학회지

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.

Urinary Transforming Growth Factor-beta1 (TGF-beta1)/Creatinine Ratio and Its Clinical Implications in Childhood Acute Pyelonephritis / 대한신장학회잡지

BACKGROUND: Pyelonephritis is one of the major causes of chronic renal failure in children, and the transforming growth factor-beta1 (TGF-beta1) is a molecule with pivotal roles in fibrogenesis. This study was performed to investigate the alteration and clinical implications of urinary TGF-beta1/creatinine ratio in children with acute pyelonephritis. METHODS: Urine was collected from 67 normal children and 25 children with acute pyelonephritis. After routine urinalysis, urine TGF-beta1 was quantitated by ELISA method and creatinine was measured by alkaline picrate method. Urinary TGF-beta1/ creatinine ratios in children with pyelonephritis were compared with those of age-matched controls, and sequential changes of the ratios in pyelonephritic children were traced after antibiotic treatment. Correlation of urinary TGF-beta1/creatinine ratio with the degree of pyuria and renal scar was analyzed each. RESULTS: Neonates showed higher urinary TGF-beta1/creatinine ratios than older children. The ratio increased in acute pyelonephritis and gradually returned to the control level two days after antibiotic treatment. Urinary TGF-beta1/creatinine ratio in acute pyelonephritis was not correlated with the degree of pyuria and renal scar. CONCLUSION: The age should be considered in evaluation of urinary TGF-beta1/creatinine ratio in children. The ratio increases in acute pyelonephritis, and is independent of the degree of pyuria or renal scarring.

Antifibrotic Effects of Phosphodiesterase (PDE) Inhibitor in Experimental Interstitial Fibrosis induced by Unilateral Ureteral Obstruction

PURPOSE: Phosphodiesterase (PDE) inhibitor increases the cellular content of cAMP, and cAMP suppresses connective tissue growth factor (CTGF) expression induced by TGF-beta1. Therefore, we investigated whether PDE inhibitor suppresses renal fibrosis without suppression of TGF-beta. MATERIALS AND METHODS: Renal interstitial fibrosis was produced by ligation of left ureter in Sprague-Dawley rats. Cilostazol, a selective PDE3 inhibitor, and dipyridamole, a hybrid PDE5, PDE6, and PDE8 inhibitor, were provided in drinking water for 7 days. In addition to the Masson-trichrome score of renal tissue, the concentration of fibronectin and TGF-beta1 in renal tissue-conditioned media was measured by ELISA. RESULTS: Masson-trichrome score and fibronectin concentration were significantly lower in cilostazol-treated group compared to the control group (P<0.05). Though dipyridamole treatment seemed to suppress the Masson-trichrome score and fibronectin concentration too, the decrements were not statistically significant. There was no difference in TGF-beta1 concentration among the groups. CONCLUSION: A selective PDE3 inhibitor cilostazol suppresses renal fibrosis without alteration of TGF-beta expression.