Interleukin‑1β increases the risk of gastric cancer through induction of aberrant DNA methylation in a mouse model

Huang,Fung‑Yu; Chan,Annie On‑On; Rashid,Asif; Wong,Danny Ka‑Ho; Seto,Wai‑Kay; Cho,Chi‑Hin; Lai,Ching‑Lung; Yuen,Man‑Fung

doi:10.3892/ol.2016.4296

Interleukin‑1β increases the risk of gastric cancer through induction of aberrant DNA methylation in a mouse model

Authors:
- Fung‑Yu Huang
- Annie On‑On Chan
- Asif Rashid
- Danny Ka‑Ho Wong
- Wai‑Kay Seto
- Chi‑Hin Cho
- Ching‑Lung Lai
- Man‑Fung Yuen
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Affiliations: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, SAR, P.R. China, Department of Pathology, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA, School of Biomedical Sciences and Institute of Digestive Diseases, Faculty of Medicine, The Chinese University of Hong Kong, SAR, P.R. China
Published online on: March 1, 2016 https://doi.org/10.3892/ol.2016.4296
Pages: 2919-2924

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Abstract

Interleukin‑1β (IL‑1β) has a significant role in chronic gastric inflammation and manifestations of gastric diseases. The present study aimed to elucidate the specific role of IL‑1β in induction of DNA methylation using IL‑1 receptor type 1 knockout (IL‑1R1‑/‑) mice. In the present study, wild‑type (WT) and IL‑1R1‑/‑ mice were injected with IL‑1β (5 µg/kg/day). Serum levels of IL‑1β, interleukin‑6 (IL‑6) and nitric oxide (NO) were measured by enzyme‑linked immunosorbent or NO assays. E‑cadherin (E‑cad) methylation status and messenger (m)RNA expression of IL‑1β, IL‑6, E‑cad and inducible nitric oxide synthase (iNOS) were analyzed. Results from the present study indicated significantly higher IL‑1β mRNA expression (P<0.001) in WT mice compared with IL‑1R1‑/‑ mice. IL‑1β and IL‑6 release was significantly increased in treated WT mice compared with IL‑1R1‑/‑ mice at 1 h, 4 h and 8 h (all P<0.005). IL‑1β release was only detected in WT mice following a second dose measured at day 3, week 1 and week 2 when compared with IL‑1R1‑/‑ mice. Promoter methylation of E‑cad and a decrease in gene expression was observed in treated WT mice. mRNA expression of iNOS in WT mice was significantly increased at week 1 compared with IL‑1R1‑/‑ mice (P=0.0411). Furthermore, a significantly increased level of NO production was observed in treated WT mice (P<0.005 at 8 h and week 1; P<0.001 at 4 h and day 3) when compared with IL‑1R1‑/‑ mice. The present results indicated that IL‑1β was able to directly induce DNA methylation, which may link inflammation‑induced epigenetic changes and the development of gastric diseases.

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1	Mantovani A, Marchesi F, Portal C, Allavena P and Sica A: Linking inflammation reactions to cancer: Novel targets for therapeutic strategies. Adv Exp Med Biol. 610:112–127. 2008. View Article : Google Scholar : PubMed/NCBI
2	Mantovani A, Allavena P, Sica A and Balkwill F: Cancer-related inflammation. Nature. 454:436–444. 2008. View Article : Google Scholar : PubMed/NCBI
3	March CJ, Mosley B, Larsen A, et al: Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature. 315:641–647. 1985. View Article : Google Scholar : PubMed/NCBI
4	Noach LA, Bosma NB, Jansen J, et al: Mucosal tumor necrosis factor-α, interleukin-1 β, and interleukin-8 production in patients with Helicobacter pylori infection. Scand J Gastroenterol. 29:425–429. 1994. View Article : Google Scholar : PubMed/NCBI
5	Huang FY, Chan AO, Lo RC, et al: Characterization of interleukin-1β in Helicobacter pylori-induced gastric inflammation and DNA methylation in interleukin-1 receptor type 1 knockout (IL-1R1(−/-)) mice. Eur J Cancer. 49:2760–2770. 2013. View Article : Google Scholar : PubMed/NCBI
6	Shigematsu Y, Niwa T, Rehnberg E, et al: Interleukin-1β induced by Helicobacter pylori infection enhances mouse gastric carcinogenesis. Cancer Lett. 340:141–147. 2013. View Article : Google Scholar : PubMed/NCBI
7	Tu S, Bhagat G, Cui G, et al: Overexpression of interleukin-1β induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice. Cancer Cell. 14:408–419. 2008. View Article : Google Scholar : PubMed/NCBI
8	Kohase M, May LT, Tamm I, Vilcek J and Sehgal PB: A cytokine network in human diploid fibroblasts: Interactions of β-interferons, tumor necrosis factor, platelet-derived growth factor, and interleukin-1. Mol Cell Biol. 7:273–280. 1987. View Article : Google Scholar : PubMed/NCBI
9	Jaiswal M, LaRusso NF and Gores GJ: Nitric oxide in gastrointestinal epithelial cell carcinogenesis: Linking inflammation to oncogenesis. Am J Physiol Gastrointest Liver Physiol. 281:G626–G634. 2001.PubMed/NCBI
10	Wink DA and Mitchell JB: Nitric oxide and cancer: An introduction. Free Radic Biol Med. 34:951–954. 2003. View Article : Google Scholar : PubMed/NCBI
11	Chan AO, Lam SK, Wong BC, et al: Promoter methylation of E-cadherin gene in gastric mucosa associated with Helicobacter pylori infection and in gastric cancer. Gut. 52:502–506. 2003. View Article : Google Scholar : PubMed/NCBI
12	Park SY, Yoo EJ, Cho NY, Kim N and Kang GH: Comparison of CpG island hypermethylation and repetitive DNA hypomethylation in premalignant stages of gastric cancer, stratified for Helicobacter pylori infection. J Pathol. 219:410–416. 2009. View Article : Google Scholar : PubMed/NCBI
13	Maekita T, Nakazawa K, Mihara M, et al: High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk. Clin Cancer Res. 12:989–995. 2006. View Article : Google Scholar : PubMed/NCBI
14	Choi IS and Wu TT: Epigenetic alterations in gastric carcinogenesis. Cell Res. 15:247–254. 2005. View Article : Google Scholar : PubMed/NCBI
15	Chan AO, Peng JZ, Lam SK, et al: Eradication of Helicobacter pylori infection reverses E-cadherin promoter hypermethylation. Gut. 55:463–468. 2006. View Article : Google Scholar : PubMed/NCBI
16	Hmadcha A, Bedoya FJ, Sobrino F and Pintado E: Methylation-dependent gene silencing induced by interleukin 1β via nitric oxide production. J Exp Med. 190:1595–1604. 1999. View Article : Google Scholar : PubMed/NCBI
17	Qian X, Huang C, Cho CH, Hui WM, Rashid A and Chan AO: E-cadherin promoter hypermethylation induced by interleukin-1β treatment or H. pylori infection in human gastric cancer cell lines. Cancer Lett. 263:107–113. 2008. View Article : Google Scholar : PubMed/NCBI
18	Huang FY, Chan AO, Rashid A, et al: Helicobacter pylori induces promoter methylation of E-cadherin via interleukin-1β activation of nitric oxide production in gastric cancer cells. Cancer. 118:4969–4980. 2012. View Article : Google Scholar : PubMed/NCBI
19	Kwon KH, Murakami A, Hayashi R and Ohigashi H: Interleukin-1β targets interleukin-6 in progressing dextran sulfate sodium-induced experimental colitis. Biochem Biophys Res Commun. 337:647–654. 2005. View Article : Google Scholar : PubMed/NCBI
20	Huang H, Ushijima T, Nagao M, Sugimura T and Ohgaki H: β-catenin mutations in liver tumors induced by 2-amino-3,4-dimethylimidazo[4,5-f]quinoline in CDF1 mice. Cancer Lett. 198:29–35. 2003. View Article : Google Scholar : PubMed/NCBI
21	Yamada H, Vijayachandra K, Penner C and Glick A: Increased sensitivity of transforming growth factor (TGF) β 1 null cells to alkylating agents reveals a novel link between TGFβ signaling and O(6)-methylguanine methyltransferase promoter hypermethylation. J Biol Chem. 276:19052–19058. 2001. View Article : Google Scholar : PubMed/NCBI
22	Livak and Schmittgen: Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCt method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
23	Chan AO, Chu KM, Huang C, et al: Association between Helicobacter pylori infection and interleukin 1β polymorphism predispose to CpG island methylation in gastric cancer. Gut. 56:595–597. 2007. View Article : Google Scholar : PubMed/NCBI
24	Griess P: Comments on the discussion of HH Weselsky and Benedict ‘On some Azo Compounds’. Ber Deutsch Chem Ges. 12:426–428. 1879. View Article : Google Scholar
25	Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 72:248–254. 1976. View Article : Google Scholar : PubMed/NCBI
26	Epstein NJ, Warme BA, Spanogle J, et al: Interleukin-1 modulates periprosthetic tissue formation in an intramedullary model of particle-induced inflammation. J Orthop Res. 23:501–510. 2005. View Article : Google Scholar : PubMed/NCBI
27	El-Omar EM: The importance of interleukin 1β in Helicobacter pylori associated disease. Gut. 48:743–747. 2001. View Article : Google Scholar : PubMed/NCBI
28	Skelly DT, Hennessy E, Dansereau MA and Cunningham C: A systematic analysis of the peripheral and CNS effects of systemic LPS, IL-1β, TNF-β and IL-6 challenges in C57BL/6 mice. PloS One. 8:e691232013. View Article : Google Scholar : PubMed/NCBI
29	Klapproth J, Castell J, Geiger T, Andus T and Heinrich PC: Fate and biological action of human recombinant interleukin 1 β in the rat in vivo. Eur J Immunol. 19:1485–1490. 1989. View Article : Google Scholar : PubMed/NCBI
30	Hur K, Niwa T, Toyoda T, et al: Insufficient role of cell proliferation in aberrant DNA methylation induction and involvement of specific types of inflammation. Carcinogenesis. 32:35–41. 2011. View Article : Google Scholar : PubMed/NCBI
31	Attwood J and Richardson B: Relative quantitation of DNA methyltransferase mRNA by real-time RT-PCR assay. Methods Mol Biol. 287:273–283. 2004.PubMed/NCBI
32	Kanai Y and Hirohashi S: Alterations of DNA methylation associated with abnormalities of DNA methyltransferases in human cancers during transition from a precancerous to a malignant state. Carcinogenesis. 28:2434–2442. 2007. View Article : Google Scholar : PubMed/NCBI
33	Nakajima T, Yamashita S, Maekita T, et al: The presence of a methylation fingerprint of Helicobacter pylori infection in human gastric mucosae. Int J Cancer. 124:905–910. 2009. View Article : Google Scholar : PubMed/NCBI
34	Niwa T, Tsukamoto T, Toyoda T, et al: Inflammatory processes triggered by Helicobacter pylori infection cause aberrant DNA methylation in gastric epithelial cells. Cancer Res. 70:1430–1440. 2010. View Article : Google Scholar : PubMed/NCBI