Expression and significance of nuclear factor kappaB p65 in colon tissues of rats with TNBS-induced colitis.
OBJECTIVE
To investigate the role of NF-kappaB in the pathogenesis of TNBS-induced colitis in rats.


METHODS
Thirty-two healthy adult Sprague-Dawley (SD) rats were randomly divided into four groups of eight each: normal, NS, model I, model II groups in our study. Rat colitis model was established through 2-,4-,6-trinitrobenzene sulfonic acid (TNBS) enema. At the end of four weeks, the macroscopical and histological changes of the colon were examined and mucosa myeloperoxidase (MPO) activities assayed. NF-kappaB p65 expression was determined by Western blot assessment in cytoplasmic and nuclear extracts of colon tissue, and the expressions of TNF-alpha and ICAM-1 protein in colon tissue were examined by immunohistochemistry. The relativities between expression of NF-kappaB p65 and other parameters were analyzed.


RESULTS
TNBS enema resulted in pronounced pathological changes of colonic mucosa in model II group (macroscopic and histological injury indices 6.25+/-1.39 and 6.24+/-1.04, respectively), which were in accordance with the significantly elevated MPO activity (1.69+/-0.11). And the nuclear level of NF-kappaB and expression of TNF-alpha, ICAM-1 in rats of model II group were higher than that of normal control (9.7+/-1.96 vs 1.7+/-0.15, 84.09+/-14.52 vs 16.03+/-6.21, 77.69+/-8.09 vs 13.41+/-4.91 P<0.01), Linear correlation analysis revealed that there were strong correlations between the nuclear level of NF-kappaB and the tissue positive expression of TNF-alpha and ICAM-1, MPO activities, macroscopical and histological indices in TNBS-induced colitis, respectively (r = 0.8235, 0.8780, 0.8572, 0.9152, 0.8247; P<0.05).


CONCLUSIONS
NF-kappaB plays a pivotal role in the pathogenesis of ulcerative colitis, which might account for the up-regulation the expression of TNF-alpha and ICAM-1.
Li
Jun-Hua
JH
Department of Gastroenterology, The Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China. lijunhua@tom.com
Yu
Jie-Ping
JP
Yu
Hong-Gang
HG
Xu
Xi-Ming
XM
Yu
Liang-Liang
LL
Liu
Shi-Quan
SQ
D000818:Animals; D015153:Blotting, Western; D003092:Colitis / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism*; D003106:Colon / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051996:Transcription Factor RelA; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016328:NF-kappa B; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase