Role of nuclear factor-kappaB in gastric ulcer healing in rats.
We investigated the role of nuclear factor-kappaB (NF-kappaB) in gastric ulcer healing in rats. NF-kappaB was activated in ulcerated tissue but not in normal mucosa, and the level of the activation was decreased with ulcer healing. NF-kappaB activation was observed in fibroblasts, monocytes/macrophages, and neutrophils. Treatment of gastric fibroblasts, isolated from the ulcer base, with interleukin-1beta activated NF-kappaB and the subsequently induced cyclooxygenase-2 and cytokine-induced neutrophil chemoattractant-1 (CINC-1) mRNA expression. Inhibition of activated NF-kappaB action resulted in suppression of both their mRNA expression and increases in PGE(2) and CINC-1 levels induced by interleukin-1beta. Persistent prevention of NF-kappaB activation caused an impairment of ulcer healing in rats. Gene expression of interleukin-1beta, 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 PGE(2) production were also reduced. These results demonstrate that NF-kappaB, activated in ulcerated tissue, might upregulate the expression of healing-promoting factors responsible for gastric ulcer healing in rats.
Takahashi
S
S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Misahagi, Yamashina, Kyoto 607-8414, Japan. takahasi@mb.kyoto-phu.ac.jp
Fujita
T
T
Yamamoto
A
A
D000818:Animals; D002478:Cells, Cultured; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013276:Stomach Ulcer / Q000503:physiopathology*; D013859:Thiocarbamates / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513297:Cxcl1 protein, rat; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D007527:Isoenzymes; D016328:NF-kappa B; D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases