Role of nuclear factor-kB in gastric ulcer healing in rats

Takahashi, Satoru, Takuya Fujita, and Akira Yamamoto. Role of nuclear factor-kB in gastric ulcer healing in rats. Am J Physiol Gastrointest Liver Physiol 280: G1296–G1304, 2001.—We investigated the role of nuclear factor-kB (NF-kB) in gastric ulcer healing in rats. NF-kB was activated in ulcerated tissue but not in normal mucosa, and the level of the activation was decreased with ulcer healing. NF-kB activation was observed in fibroblasts, monocytes/ macrophages, and neutrophils. Treatment of gastric fibroblasts, isolated from the ulcer base, with interleukin-1b activated NF-kB and the subsequently induced cyclooxygenase-2 and cytokine-induced neutrophil chemoattractant-1 (CINC-1) mRNA expression. Inhibition of activated NF-kB action resulted in suppression of both their mRNA expression and increases in PGE2 and CINC-1 levels induced by interleukin1b. Persistent prevention of NF-kB activation caused an impairment of ulcer healing in rats. Gene expression of interleukin-1b, 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-kB, activated in ulcerated tissue, might upregulate the expression of healing-promoting factors responsible for gastric ulcer healing in rats.