白介素-1β誘導胃上皮細胞GES-1表達腸道特異性標志物_《中國普外基礎與臨床雜志》

作者：

孫仁虎 , 李疆 , 童強 , 舒曉剛 , 王國斌

華中科技大學同濟醫學院附屬協和醫院胃腸外科（武漢　430022）;

關鍵詞：

白細胞介素-1β 腸上皮化生尾側型同源轉錄因子-1 黏蛋白-2 核因子-κB 胃癌癌前病變

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目的觀察白細胞介素-1β（IL-1β）對體外培養的人胃黏膜上皮GES-1細胞中腸道特異性標志物尾側型同源轉錄因子-1（CDX1）和腸道黏蛋白-2（MUC2）表達的誘導作用，探討其作用機理。方法通過不同濃度及不同作用時間的IL-1β刺激人胃黏膜上皮GES-1細胞，采用實時定量PCR法檢測CDX1 mRNA和MUC2 mRNA的表達水平；　并使用NF-κB抑制劑PDTC預處理GES-1細胞，檢測PDTC對IL-1β誘導的CDX1 mRNA和MUC2 mRNA表達水平的影響。結果正常情況下人胃黏膜上皮GES-1細胞不表達CDX1 mRNA和MUC2 mRNA，而IL-1β可以誘導GES-1細胞中CDX1 mRNA和MUC2 mRNA的表達，該作用在一定濃度范圍內呈現劑量依賴性（P＜0.05）；　IL-1β作用8 h時，CDX1 mRNA和MUC2 mRNA的表達達到峰值（P＜0.05），隨后表達逐漸降低。經NF-κB抑制劑PDTC預處理后的GES-1細胞，CDX1 mRNA和MUC2 mRNA的表達水平明顯下降（P＜0.05）。結論 IL-1β可能通過NF-κB信號通路促進人胃黏膜上皮細胞中CDX1 mRNA和MUC2 mRNA的表達，在胃黏膜腸上皮化生中發揮作用。

引用本文： 孫仁虎,李疆,童強,舒曉剛,王國斌. 白介素-1β誘導胃上皮細胞GES-1表達腸道特異性標志物. 中國普外基礎與臨床雜志, 2009, 16(5): 370-374. doi: 復制

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2.	Wong NA, Wilding J, Bartlett S, et al. CDX1 is an important molecular mediator of Barrett’s metaplasia [J]. Proc Natl Acad Sci USA, 2005; 102(21): 7565-7570.
3.	Babu SD, Jayanthi V, Devaraj N, et al. Expression profile of mucins (MUC2, MUC5AC and MUC6) in Helicobacter pylori infected pre-neoplastic and neoplastic human gastric epithelium [J]. Mol Cancer, 2006; 5: 10.
4.	Sutton P, Kolesnikow T, Danon S, et al. Dominant nonresponsiveness to Helicobacter pylori infection is associated with production of interleukin 10 but not gamma interferon [J]. Infect Immun, 2000; 68(8): 4802-4804.
5.	Rad R, Prinz C, Neu B, et al. Synergistic effect of Helicobacter pylori virulence factors and interleukin-1 polymorphisms for the development of severe histological changes in the gastric mucosa [J]. J Infect Dis, 2003; 188(2): 272-281.
6.	Shimoyama T, Fukuda S, Tanaka M, et al. Evaluation of the applicability of the gastric carcinoma risk index for intestinal type cancer in Japanese patients infected with Helicobacter pylori [J]. Virchows Arch, 2000; 436(6): 585-587.
7.	Walker MM. Is intestinal metaplasia of the stomach reversible? [J]. Gut, 2003; 52(1): 1-4.
8.	Robert A, Saperas E, Zhang WR, et al. Gastric cytoprotection by intracisternal interleukin-1 beta in the rat [J]. Biochem Biophys Res Commun, 1991; 174(3): 1117-1124.
9.	Wang M, Furuta T, Takashima M, et al. Relation between interleukin-1beta messenger RNA in gastric fundic mucosa and gastric juice pH in patients infected with Helicobacter pylori [J]. J Gastroenterol, 1999; 34(Suppl 11): 10-17.
10.	Robert A, Olafsson AS, Lancaster C, et al. Interleukin-1 is cytoprotective, antisecretory, stimulates PGE2 synthesis by the stomach, and retards gastric emptying [J]. Life Sci, 1991; 48(2): 123-134.
11.	Serrano MT, Lanas AI, Lorente S, et al. Cytokine effects on pepsinogen secretion from human peptic cells [J]. Gut, 1997; 40(1): 42-48.
12.	Sutton P, Kolesnikow T, Danon S, et al. Dominant nonresponsiveness to Helicobacter pylori infection is associated with production of interleukin 10 but not gamma interferon [J]. Infect Immun, 2000; 68(8): 4802-4804.
13.	Fox JG, Beck P, Dangler CA, et al. Concurrent enteric helminth infection modulates inflammation and gastric immune responses and reduces helicobacter-induced gastric atrophy [J]. Nat Med, 2000; 6(5): 536-542.
14.	Stoicov C, Whary M, Rogers AB, et al. Coinfection modulates inflammatory responses and clinical outcome of Helicobacter felis and Toxoplasma gondii infections [J]. J Immunol, 2004; 173(5): 3329-3336.
15.	Zeng ZR, Hu PJ, Hu S, et al. Association of interleukin 1B gene polymorphism and gastric cancers in high and low prevalence regions in China [J]. Gut, 2003; 52(12): 1684-1689.
16.	Yang J, Hu Z, Xu Y, et al. Interleukin-1B gene promoter variants are associated with an increased risk of gastric cancer in a Chinese population [J]. Cancer Lett, 2004; 215(2): 191-198.
17.	Lu W, Pan K, Zhang L, et al. Genetic polymorphisms of interleukin (IL)-1B, IL-1RN, IL-8, IL-10 and tumor necrosis factor α and risk of gastric cancer in a Chinese population [J]. Carcinogenesis, 2005; 26(3): 631-636.
18.	Leung WK, Chan MC, To KF, et al. H.pylori genotypes and cytokine gene polymorphisms influence the development of gastric intestinal metaplasia in a Chinese population [J]. Am J Gastroenterol, 2006; 101(4): 714-720.
19.	Silberg DG, Furth EE, Taylor JK, et al. CDX1 protein expression in normal, metaplastic, and neoplastic human alimentary tract epithelium [J]. Gastroenterology, 1997; 113(2): 478-486.
20.	Freund JN, Domon-Dell C, Kedinger M, et al. The Cdx-1 and Cdx-2 homeobox genes in the intestine [J]. Biochem Cell Biol, 1998; 76(6): 957-969.
21.	Mutoh H, Sakurai S, Satoh K, et al. Cdx1 induced intestinal metaplasia in the transgenic mouse stomach: comparative study with Cdx2 transgenic mice [J]. Gut, 2004; 53(10): 1416-1423.
22.	Reis CA, David L, Correa P, et al. Intestinal metaplasia of human stomach displays distinct patterns of mucin (MUC1, MUC2, MUC5AC, and MUC6) expression [J]. Cancer Res, 1999; 59(5): 1003-1007.
23.	Ho SB, Shekels LL, Toribara NW, et al. Mucin gene expression in normal, preneoplastic, and neoplastic human gastric epithelium [J]. Cancer Res, 1995; 55(12): 2681-2690.
24.	Enss ML, Cornberg M, Wagner S, et al. Proinflammatory cytokines trigger MUC gene expression and mucin release in the intestinal cancer cell line LS180 [J]. Inflamm Res, 2000; 49(4): 162-169.
25.	Thomas JA, Allen JL, Tsen M, et al. Impaired cytokine signaling in mice lacking the IL-1 receptor-associated kinase [J]. J Immunol, 1999; 163(2): 978-984.

1. Correa P, Haenszel W, Cuello C, et al. A model for gastric cancer epidemiology [J]. Lancet, 1975; 2(7924): 58-60.
2. Wong NA, Wilding J, Bartlett S, et al. CDX1 is an important molecular mediator of Barrett’s metaplasia [J]. Proc Natl Acad Sci USA, 2005; 102(21): 7565-7570.
3. Babu SD, Jayanthi V, Devaraj N, et al. Expression profile of mucins (MUC2, MUC5AC and MUC6) in Helicobacter pylori infected pre-neoplastic and neoplastic human gastric epithelium [J]. Mol Cancer, 2006; 5: 10.
4. Sutton P, Kolesnikow T, Danon S, et al. Dominant nonresponsiveness to Helicobacter pylori infection is associated with production of interleukin 10 but not gamma interferon [J]. Infect Immun, 2000; 68(8): 4802-4804.
5. Rad R, Prinz C, Neu B, et al. Synergistic effect of Helicobacter pylori virulence factors and interleukin-1 polymorphisms for the development of severe histological changes in the gastric mucosa [J]. J Infect Dis, 2003; 188(2): 272-281.
6. Shimoyama T, Fukuda S, Tanaka M, et al. Evaluation of the applicability of the gastric carcinoma risk index for intestinal type cancer in Japanese patients infected with Helicobacter pylori [J]. Virchows Arch, 2000; 436(6): 585-587.
7. Walker MM. Is intestinal metaplasia of the stomach reversible? [J]. Gut, 2003; 52(1): 1-4.
8. Robert A, Saperas E, Zhang WR, et al. Gastric cytoprotection by intracisternal interleukin-1 beta in the rat [J]. Biochem Biophys Res Commun, 1991; 174(3): 1117-1124.
9. Wang M, Furuta T, Takashima M, et al. Relation between interleukin-1beta messenger RNA in gastric fundic mucosa and gastric juice pH in patients infected with Helicobacter pylori [J]. J Gastroenterol, 1999; 34(Suppl 11): 10-17.
10. Robert A, Olafsson AS, Lancaster C, et al. Interleukin-1 is cytoprotective, antisecretory, stimulates PGE2 synthesis by the stomach, and retards gastric emptying [J]. Life Sci, 1991; 48(2): 123-134.
11. Serrano MT, Lanas AI, Lorente S, et al. Cytokine effects on pepsinogen secretion from human peptic cells [J]. Gut, 1997; 40(1): 42-48.
12. Sutton P, Kolesnikow T, Danon S, et al. Dominant nonresponsiveness to Helicobacter pylori infection is associated with production of interleukin 10 but not gamma interferon [J]. Infect Immun, 2000; 68(8): 4802-4804.
13. Fox JG, Beck P, Dangler CA, et al. Concurrent enteric helminth infection modulates inflammation and gastric immune responses and reduces helicobacter-induced gastric atrophy [J]. Nat Med, 2000; 6(5): 536-542.
14. Stoicov C, Whary M, Rogers AB, et al. Coinfection modulates inflammatory responses and clinical outcome of Helicobacter felis and Toxoplasma gondii infections [J]. J Immunol, 2004; 173(5): 3329-3336.
15. Zeng ZR, Hu PJ, Hu S, et al. Association of interleukin 1B gene polymorphism and gastric cancers in high and low prevalence regions in China [J]. Gut, 2003; 52(12): 1684-1689.
16. Yang J, Hu Z, Xu Y, et al. Interleukin-1B gene promoter variants are associated with an increased risk of gastric cancer in a Chinese population [J]. Cancer Lett, 2004; 215(2): 191-198.
17. Lu W, Pan K, Zhang L, et al. Genetic polymorphisms of interleukin (IL)-1B, IL-1RN, IL-8, IL-10 and tumor necrosis factor α and risk of gastric cancer in a Chinese population [J]. Carcinogenesis, 2005; 26(3): 631-636.
18. Leung WK, Chan MC, To KF, et al. H.pylori genotypes and cytokine gene polymorphisms influence the development of gastric intestinal metaplasia in a Chinese population [J]. Am J Gastroenterol, 2006; 101(4): 714-720.
19. Silberg DG, Furth EE, Taylor JK, et al. CDX1 protein expression in normal, metaplastic, and neoplastic human alimentary tract epithelium [J]. Gastroenterology, 1997; 113(2): 478-486.
20. Freund JN, Domon-Dell C, Kedinger M, et al. The Cdx-1 and Cdx-2 homeobox genes in the intestine [J]. Biochem Cell Biol, 1998; 76(6): 957-969.
21. Mutoh H, Sakurai S, Satoh K, et al. Cdx1 induced intestinal metaplasia in the transgenic mouse stomach: comparative study with Cdx2 transgenic mice [J]. Gut, 2004; 53(10): 1416-1423.
22. Reis CA, David L, Correa P, et al. Intestinal metaplasia of human stomach displays distinct patterns of mucin (MUC1, MUC2, MUC5AC, and MUC6) expression [J]. Cancer Res, 1999; 59(5): 1003-1007.
23. Ho SB, Shekels LL, Toribara NW, et al. Mucin gene expression in normal, preneoplastic, and neoplastic human gastric epithelium [J]. Cancer Res, 1995; 55(12): 2681-2690.
24. Enss ML, Cornberg M, Wagner S, et al. Proinflammatory cytokines trigger MUC gene expression and mucin release in the intestinal cancer cell line LS180 [J]. Inflamm Res, 2000; 49(4): 162-169.
25. Thomas JA, Allen JL, Tsen M, et al. Impaired cytokine signaling in mice lacking the IL-1 receptor-associated kinase [J]. J Immunol, 1999; 163(2): 978-984.

《中國普外基礎與臨床雜志》

白介素-1β誘導胃上皮細胞GES-1表達腸道特異性標志物

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《中國普外基礎與臨床雜志》

白介素-1β誘導胃上皮細胞GES-1表達腸道特異性標志物

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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