ACTIVATION OF TRANSCRIPTION FACTOR NF-KAPPA-B IN EXPERIMENTAL GLOMERULONEPHRITIS IN RATS

NF-kappa B plays a pivotal role in cells of the immune system as an in ducible transcriptional activator. NF-kappa B regulates the transcript ion of many genes of pro-inflammatory cytokines and cell adhesion mole cules, which could be involved in the pathogenesis of glomerulonephrit is. Using a gel shift assay, we investigated NF-kappa B DNA-binding ac tivity in glomeruli of WKY rats injected with nephrotoxic serum (NTS). Kinetic analysis indicated that the NF-kappa B DNA-binding activity i n glomeruli, composed of p50 subunit determined by a supershift assay, increased on day I after NTS injection and the maximal activation was observed on day 3 to 5. NF-kappa B activation persisted at least unti l day 14. Pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of NF -kappa B activation, inhibited the NTS-induced increase of glomerular NF-kappa B DNA-binding activity, followed by the inhibition of mRN4 ex pression of IL-1 beta, MCP-1, ICAM-1 and iNOS, which are known to be r egulated by NF-kappa B. PDTC also prevented urinary protein excretion which is a pathophysiological parameter for glomerulonephritis. These results suggest that NF-kappa B activation causes the induction of pro -inflammatory factors in nephritic glomeruli, which may play significa nt roles in the pathogenesis of glomerulonephritis.