2002 Fiscal Year Final Research Report Summary
Induction of EGF-like Growth Factors and Epidermal Growth Factor Receptors by Interleukin-1β in Gastric Mucosa
| Project/Area Number |
13670570
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Nippon Medical School |
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Principal Investigator |
WADA Ken Third Department of Internal Medicine, Nippon Medical School, Research Associates, 医学部, 助手 (30307954)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAMOTO Choitsu Third Department of Internal Medicine, Nippon Medical School, Professor, 医学部, 教授 (30196092)
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| Project Period (FY) |
2001 – 2002
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| Keywords | IL-1 / TGF-α / EGF-like growth factor / gastritis / gastric fibroblast |
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| Research Abstract |
In this sturdy, we hypothesized IL-1β, proinflammatory cytokine, could exert some biological effects through expression of epidermal growth factor (EOF) family peptides in gastric mucosa. Therefore we examined the ability of IL-1β to induce EGF-like growth factors and EGF receptor (EGFR) in human gastric fibrodasts and 5 gastric cancer cell lines. Methods: Cultured cells were stimulated by IL-1β and the mRNA expression of transforming growth factor-α (TGF-α), heparin-binding EGF-like growth factor (HB-EGF) and amphiregulin (AR) was examined by real-time PCR. TGF-α in the conditioned media (CM) obtained from culture cells was determined using a TGF-α ELISA kit. EGFR expression was examined by western blot analysis. Results: IL-1β increased mRNA levels of TGF-α, HB-EGF and AR in 4 gastric cancer cell lines. In contrast, a significant expression of TGF-α mRNA was not found in gastric fibroblasts. In the 4 gastric cancer cell lines, IL-1β stimulated TGF-α release into CM only in the presen
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ce of 12-myristate 13-acetate (PMA), which is known to induce a cleavaging enzyme of proTGF-α. Selective COX-2 inhibitors did not inhibit the TGF-α release by IL-1β, suggesting that this induction of TGF-α was not mediated by COX-2. Furthermore, IL-1β increased TGF-α expression more significantly in coculture of MKN28 cells and gastric fibroblasts than in separate cultivation, indicating there might be some epithelial-mesenchymal interaction in TGF-α induction by IL-1β. CM from gastric fibroblasts incubated with IL-1β stimulated TGF-α expression in MKN28 cells more significantly than control media, confirming our assumption. Contrary to TGF-α expression, IL-1β increased expression of EGFR in gastric fibroblasts, but not in MKN28 cells. Furthermore, IL-1β activated tyrosine phosphorylation of EGFR in coculture of MKN28 cells and gastric fibroblasts more markedly than in separate cultivation. Conclusion: IL-1β exerts its biological effects on the gastric mucosa through the induction of EGFR and EGF-like growth factors in epithelial-mesenchymal interaction. Less
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Research Products
(6 results)
