• 華中科技大學(xué)同濟(jì)醫(yī)學(xué)院附屬協(xié)和醫(yī)院胃腸外科（武漢　430022）;

目的  觀察白細(xì)胞介素-1β（IL-1β）對(duì)體外培養(yǎng)的人胃黏膜上皮GES-1細(xì)胞中腸道特異性標(biāo)志物尾側(cè)型同源轉(zhuǎn)錄因子-1（CDX1）和腸道黏蛋白-2（MUC2）表達(dá)的誘導(dǎo)作用，探討其作用機(jī)理。方法  通過(guò)不同濃度及不同作用時(shí)間的IL-1β刺激人胃黏膜上皮GES-1細(xì)胞，采用實(shí)時(shí)定量PCR法檢測(cè)CDX1 mRNA和MUC2 mRNA的表達(dá)水平；　并使用NF-κB抑制劑PDTC預(yù)處理GES-1細(xì)胞，檢測(cè)PDTC對(duì)IL-1β誘導(dǎo)的CDX1 mRNA和MUC2 mRNA表達(dá)水平的影響。結(jié)果  正常情況下人胃黏膜上皮GES-1細(xì)胞不表達(dá)CDX1 mRNA和MUC2 mRNA，而IL-1β可以誘導(dǎo)GES-1細(xì)胞中CDX1 mRNA和MUC2 mRNA的表達(dá)，該作用在一定濃度范圍內(nèi)呈現(xiàn)劑量依賴性（P＜0.05）；　IL-1β作用8 h時(shí)，CDX1 mRNA和MUC2 mRNA的表達(dá)達(dá)到峰值（P＜0.05），隨后表達(dá)逐漸降低。經(jīng)NF-κB抑制劑PDTC預(yù)處理后的GES-1細(xì)胞，CDX1 mRNA和MUC2 mRNA的表達(dá)水平明顯下降（P＜0.05）。 結(jié)論  IL-1β可能通過(guò)NF-κB信號(hào)通路促進(jìn)人胃黏膜上皮細(xì)胞中CDX1 mRNA和MUC2 mRNA的表達(dá)，在胃黏膜腸上皮化生中發(fā)揮作用。

引用本文： 孫仁虎,李疆,童強(qiáng),舒曉剛,王國(guó)斌. 白介素-1β誘導(dǎo)胃上皮細(xì)胞GES-1表達(dá)腸道特異性標(biāo)志物. 中國(guó)普外基礎(chǔ)與臨床雜志, 2009, 16(5): 370-374. doi: 復(fù)制

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.
  1. 1. Correa P, Haenszel W, Cuello C, et al. A model for gastric cancer epidemiology [J]. Lancet, 1975; 2(7924): 58-60.
  2. 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. 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. 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. 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. 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. 7. Walker MM. Is intestinal metaplasia of the stomach reversible? [J]. Gut, 2003; 52(1): 1-4.
  8. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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.