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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Chuang
Yen-Hwang
YH
Department of Anatomy, College of Medicine, Kaohsiung Medical University, Kaohsiung 803, Taiwan.
Chuang
Wan-Long
WL
Huang
Shu-Pin
SP
Liu
Ching-Kuan
CK
Huang
Chun-Hsiung
CH
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000276:immunology; D011759:Pyrrolidines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013859:Thiocarbamates / Q000494:pharmacology / Q000627:therapeutic use*; D014513:Ureter / Q000187:drug effects* / Q000473:pathology; D014517:Ureteral Obstruction / Q000188:drug therapy* / Q000473:pathology
D000975:Antioxidants; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid