IL-1β Induces Expression of Intestinal Specific Markers in Cultured Human Gastric Epithelial Cells GES-1_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

SUN Renhu , LI Jiang , TONG Qiang , SHU Xiaogang , WANG Guobin.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China;

Corresponding author：

Keywords：

白细胞介素-1β; 肠上皮化生; 尾侧型同源转录因子-1; 黏蛋白-2; 核因子-κB; 胃癌; 癌前病变

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To observed the effect of IL-1β on expression of caudal-related homeobox gene 1 (CDX1) mRNA and mucoprotein 2 (MUC2) mRNA in cultured human gastric epithelial cells GES-1, and to investigate the underlying signal transduction pathways. Methods ①GES-1 cell was activated with IL-1β of different concentrations and time, the expression levels of CDX1 mRNA and MUC2 mRNA were detected by using real-time PCR. ②GES-1 cell was pretreated with PDTC, a NF-κB inhibitor, for 1 h prior to the addition of IL-1β, then the expressions of CDX1 mRNA and MUC2 mRNA were measured. Results Both CDX1 mRNA and MUC2 mRNA were not examined in GES-1 cell under normal culture conditions. But they could be induced by IL-1β with a dose-dependent manner in a concentration range (P＜0.05); 8 h after treatment with IL-1β, the peak values of the expression levels of CDX1 mRNA and MUC2 mRNA were reached (P＜0.05), then declined gradually. When pre-incubated with NF-κB inhibitor PDTC, the expression levels of CDX1 mRNA and MUC2 mRNA were significantly decreased (P＜0.05). Conclusion IL-1β significantly induces the expressions of CDX1 mRNA and MUC2 mRNA in cultured human gastric epithelial cell GES-1 through the NF-κB signal pathway, which indicates that IL-1β plays a role in the process of intestinal metaplasia.

Citation： SUN Renhu,LI Jiang,TONG Qiang,SHU Xiaogang,WANG Guobin.. IL-1β Induces Expression of Intestinal Specific Markers in Cultured Human Gastric Epithelial Cells GES-1. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2009, 16(5): 370-374. doi: Copy

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. 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.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

IL-1β Induces Expression of Intestinal Specific Markers in Cultured Human Gastric Epithelial Cells GES-1

Abstract Full text Figures/Tables Video References Cited by

Format

Content