title: Regulation by endogenous interleukin-1 of mRNA expression of healing-related factors in gastric ulcers in rats.
abstract: 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)-beta1 in acetic acid-induced gastric ulcers in rats. IL-1beta mRNA was not detected in the normal or intact mucosa of ulcerated stomachs, but its expression was induced in the ulcerated tissue. IL-1beta 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-beta1 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-beta1 mRNA expression was not affected by IL-1RA. IL-1RA dose-dependently reduced prostaglandin E(2) 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.
authors.affiliation: Department of Applied Pharmacology, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto, Japan. takahasi@mb.kyoto-phu.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: N
authors.initials: N
authors.lastname: Kobayashi
authors.forename: S
authors.initials: S
authors.lastname: Okabe
mesh_terms: D019342:Acetic Acid / Q000633:toxicity; D000818:Animals; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000502:physiology; D006133:Growth Substances / Q000378:metabolism; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000276:immunology / Q000502:physiology*; D008297:Male; D009504:Neutrophils / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D013276:Stomach Ulcer / Q000473:pathology*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D006133:Growth Substances; D007375:Interleukin-1; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D019342:Acetic Acid