Supperssion of the Activation of Nuclear Factor Kappa B and the Expression of Monocyte Chemoattractant Protein-1 by Glucocorticoids in Experimental Rat Glomerulonephritis

Abstract:

OBJECTIVE: To investigate the role of nuclear factor kappa B (NF-κB) in the pathogenesis of glomerulonephritis and to determine whether glucocorticoids can inhibit the activation of NF-κB in vivo. METHODS: Nephrotoxic sera nephritis (NTN) was induced by the injection of antiGBM antibody into the tail veins of rats. Glucocorticoidtreated rats received dexamethasone (0.125 mg/kg weight) daily for 14 days. Untreated and steroidtreated rats were killed on day 14 and NF-κB activation and monocyte chemoattractant protein1 (MCP-1) expression were assessed in glomerulus and renal tubules of rats. RESULTS: Significant upregulation of NF-κB activation was observed in glomerulus and renaltubules of untreated NTN rats compared to the control group ［(38.27±8.83)% vs (1.82±0.68)%; (68.46±12.94)% vs (16.89±4.47)%, repsectively］ (P<0.01), and so was the expression of MCP-1 ［(24.37±7.06) cells/gcs vs 0; (54.78±11.49)% vs (11.26±6.88)%］ (P<0.01). NF-κB activation and MCP-1 expression were associated with monocyte cell infiltration and the degree of proteinuria. Significant downregulation of NF-κB activation and MCP-1 expression were observed in the glucocorticoidtreated rats. CONCLUSIONS: The activated NF-κB may play a pivotal pathogenic role in glomerulonephritis and the antinephritic action of glucocorticoids may be mediated through the suppression of the activation of NF-κB.