| Autor: |
Fg, Brown, Dj, Nikolic-Paterson, Nm, Isbel, R, Bucala, C, Metz, Jp, Dowling, RC., Atkins |
| Předmět: |
|
| Zdroj: |
Nephrology; Oct2000, Vol. 5 Issue 3, pA95, 1p |
| Abstrakt: |
MIF is a potent proinflammatory cytokine. Renal MIF expression is markedly upregulated in rat crescentic anti-GBM GN and blocking studies have demonstrated a pathogenic role for MIF in mediating renal injury in this model. To determine the importance of MIF in human GN we performed immunostaining to localise MIF protein within biopsies and used an ELISA to measure urine and serum MIF levels. Patients studied were: 2 Thin BM disease, 15 Memb GN, 10 FSGS, 20 IgA GN, 11 Cres GN, 10 SLE Class IV and blood an urine from 10 normal volunteers. MIF protein is constitutively expressed by some glomerular epithelial cells and 40-60% of cortical tubular epithelial cells in normal human kidney. MIF protein was increased in most forms of GN, being most marked in severe proliferative GN with increased MIF expression in glomerular epithelial cells, infiltrating leukocytes and cortical tubules. The number of glomerular MIF + cells correlated with renal dysfunction (P < 0.001). The percent of MIF + tubules correlated with renal dysfunction, interstitial macrophages and T cells (all P < 0.001). Urine MIF levels were increased in Cres GN (867 ± 710 pg/umol Cr) compared to normal (186 ± 13,P < 0.05). Analysis of all patients showed that urine MIF levels correlated with renal dysfunction, glomerular macrophages, and interstitial macrophages and T cells (all P < 0.05). Urine MIF levels correlated with glomerular and tubular MIF expression (both P < 0.05). Serum levels of MIF did not vary between the groups, demonstrating that urinary MIF is derived from intrarenal production. This study shows that MIF is produced locally within the kidney by both intrinsic and infiltrating cells, reflects the severity of the cellular immune response, and can be measured in urine. This identifies MIF as a potential therapeutic target in human GN. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
