We investigated the role of nuclear factor-κB (NF-κB) in gastric ulcer healing in rats. NF-κB was activated in ulcerated tissue but not in normal mucosa, and the level of the activation was decreased with ulcer healing. NF-κB activation was observed in fibroblasts, monocytes/macrophages, and neutrophils. Treatment of gastric fibroblasts, isolated from the ulcer base, with interleukin-1β activated NF-κB and the subsequently induced cyclooxygenase-2 and cytokine-induced neutrophil chemoattractant-1 (CINC-1) mRNA expression. Inhibition of activated NF-κB action resulted in suppression of both their mRNA expression and increases in PGE2 and CINC-1 levels induced by interleukin-1β. Persistent prevention of NF-κB activation caused an impairment of ulcer healing in rats. Gene expression of interleukin-1β, 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-κB, activated in ulcerated tissue, might upregulate the expression of healing-promoting factors responsible for gastric ulcer healing in rats.
The role of thromboxane prostanoid receptor signaling in gastric ulcer healing
