Role of nuclear factor-?B in gastric ulcer healing in rats.
Takahashi, Satoru, Takuya Fujita, and Akira Yamamoto.
1Department of Applied Pharmacology and 2Department of Biopharmaceutics, Kyoto
Pharmaceutical University, Kyoto 607«hyphen»8414, Japan
APStracts 8:0049G, 2001.
We investigated the role of nuclear factor-?B (NF-?B) in gastric ulcer healing in rats.
NF-?B was activated in ulcerated tissue but not in normal mucosa, and the level of the
activation was decreased with ulcer healing. NF-?B activation was observed in
fibroblasts, monocytes/macrophages, and neutrophils. Treatment of gastric fibroblasts,
isolated from the ulcer base, with interleukin-1ß activated NF-?B and the subsequently
induced cyclooxygenase-2 and cytokine-induced neutrophil chemoattractant-1 (CINC-1)
mRNA expression. Inhibition of activated NF-?B action resulted in suppression of both
their mRNA expression and increases in PGE2 and CINC-1 levels induced by
interleukin-1ß. Persistent prevention of NF-?B activation caused an impairment of ulcer
healing in rats. Gene expression of interleukin-1ß, CINC-1, cyclooxygenase-2, and
inducible nitric oxide synthase in ulcerated tissue had been inhibited before the delay in
ulcer healing became manifest. The increased levels of cyclooxygenase-2 protein and
PGE2 production were also reduced. These results demonstrate that NF-?B, activated in
ulcerated tissue, might upregulate the expression of healing-promoting factors
responsible for gastric ulcer healing in rats.
Received 18 May 2000; accepted in final form 22 January 2001
APS Manuscript Number G212-0.
Article publication pending Am J Physiol Gastrointest Liver Physiol
ISSN 1080-4757 Copyright 2001 The American Physiological Society.
Published in APStracts on 29 March 2001