Inhibition of nuclear factor-kappa B (NF-kappaB) activation attenuates ureteric damage in obstructive uropathy

Nuclear factor (NF)-kappaB is a ubiquitous transcription factor that can be activated by multiple signals. To elucidate the role of NF-KB and the effects of NF-kappaB inhibitor on ureteric damages in obstructive uropathy, we conducted this study.

The expressions of NF-kappaBp50, NF-kappaBp65, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), proliferation cell nuclear antigen (PCNA) and cell apoptosis were examined in 80 rats. Pyrrolidine dithiocarbamate (PDTC) was administered to 40 rats. The others served as controls.

After ureteric ligation, hydroureter and ureteric damages progressively aggravated. But the severity of hydroureter and fibrosis of muscle layer in the ligated ureters in the treated group were significantly milder than those of the control group. The expressions of NF-kappaBp50 and NFkappa-Bp65 in the smooth muscle layer of obstructed ureters were found in the rats in control group from the day 14 after ureteric ligation. The expressions of NF-kappaBp65 and NF-kappaBp50 in the nuclei of muscle cells in obstructed ureters were correlated significantly with the expressions of IL-6, TNF-alpha, PCNA and the number of the apoptotic cells. The expressions of NF-kappaBp50, NF-kappaBp65 in the nuclei of myocytes and fibrotic changes of smooth muscle layer were correlated significantly. Treatment with PDTC diminished the expressions of NF-kappaBp50 and NF-kappaBp65. The expression of IL-6, TNF-alpha, PCNA and the labeling index of apoptotic cells in the smooth muscle layer of ligated ureters in the PDTC-treated group were also decreased.

We concluded that expression of NF-kappaB might contribute to the ureteric damage in obstructive uropathy, and that inhibition of NF-kB could attenuate the tissue damages of obstructed ureters.