RT Journal Article
SR Electronic
T1 Regulation by Endogenous Interleukin-1 of mRNA Expression of Healing-Related Factors in Gastric Ulcers in Rats
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 634
OP 641
VO 291
IS 2
A1 Satoru Takahashi
A1 Norihiro Kobayashi
A1 Susumu Okabe
YR 1999
UL http://jpet.aspetjournals.org/content/291/2/634.abstract
AB We investigated the role of endogenous interleukin (IL)-1 in the mRNA expression of cyclooxygenase (COX)-1, COX-2, inducible nitric oxide synthase (iNOS), cytokine-induced neutrophil chemoattractant (CINC)-1, epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and transforming growth factor (TGF)-β1 in acetic acid-induced gastric ulcers in rats. IL-1β mRNA was not detected in the normal or intact mucosa of ulcerated stomachs, but its expression was induced in the ulcerated tissue. IL-1β immunoreactivity was observed in macrophages/monocytes and fibroblasts in the ulcer base. COX-2, iNOS, and CINC-1 mRNAs were expressed by ulceration. EGF, bFGF, HGF, and TGF-β1 mRNA expression was detected in the normal mucosa, and their levels were significantly elevated by ulceration. In contrast, COX-1 mRNA level did not differ between the normal and ulcerated tissues. In a culture of isolated ulcer bases, block of IL-1 with IL-1 receptor antagonist (IL-1RA) dose-dependently and significantly reduced the mRNA levels of COX-2, iNOS, CINC-1, HGF, and bFGF. In contrast, COX-1, EGF, and TGF-β1 mRNA expression was not affected by IL-1RA. IL-1RA dose-dependently reduced prostaglandin E2 production, total and iNOS activities, neutrophil chemotactic activity, and growth-promoting activity toward gastric epithelial cells in the ulcer base. Finally, the administration of IL-1RA caused a significant impairment of ulcer healing. These results indicate that IL-1, expressed in macrophages/monocytes and fibroblasts in the ulcer base, might up-regulate the mRNA expression of COX-2, iNOS, CINC-1, HGF, and bFGF, thereby contributing to gastric ulcer healing in rats. The American Society for Pharmacology and Experimental Therapeutics