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Research ArticleArticle

Regulation by Endogenous Interleukin-1 of mRNA Expression of Healing-Related Factors in Gastric Ulcers in Rats

Satoru Takahashi, Norihiro Kobayashi and Susumu Okabe
Journal of Pharmacology and Experimental Therapeutics November 1999, 291 (2) 634-641;
Satoru Takahashi
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Norihiro Kobayashi
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Susumu Okabe
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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)-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.

Footnotes

  • Send reprint requests to: Satoru Takahashi, Ph.D., Department of Applied Pharmacology, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan. E-mail:takahasi{at}mb.kyoto-phu.ac.jp

  • Abbreviations:
    IL
    interleukin
    bp
    base pair
    COX
    cyclooxygenase
    iNOS
    inducible nitric oxide synthase
    DMEM
    Dulbecco’s modified Eagle’s medium
    CINC
    cytokine-induced neutrophil chemoattractant
    HGF
    hepatocyte growth factor
    EGF
    epidermal growth factor
    bFGF
    basic fibroblast growth factor
    GAPDH
    glyceraldehyde-3-phosphate dehydrogenase
    TGF-β1
    transforming growth factor-β1
    IL-1RA
    interleukin-1 receptor antagonist
    PG
    prostaglandin
    • Received December 15, 1998.
    • Accepted July 16, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 291 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 291, Issue 2
1 Nov 1999
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Research ArticleArticle

Regulation by Endogenous Interleukin-1 of mRNA Expression of Healing-Related Factors in Gastric Ulcers in Rats

Satoru Takahashi, Norihiro Kobayashi and Susumu Okabe
Journal of Pharmacology and Experimental Therapeutics November 1, 1999, 291 (2) 634-641;

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Research ArticleArticle

Regulation by Endogenous Interleukin-1 of mRNA Expression of Healing-Related Factors in Gastric Ulcers in Rats

Satoru Takahashi, Norihiro Kobayashi and Susumu Okabe
Journal of Pharmacology and Experimental Therapeutics November 1, 1999, 291 (2) 634-641;
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