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Article: Characterization of interleukin-1β in Helicobacter pylori-induced gastric inflammation and DNA methylation in interleukin-1 receptor type 1 knockout (IL-1R1-/-) mice

TitleCharacterization of interleukin-1β in Helicobacter pylori-induced gastric inflammation and DNA methylation in interleukin-1 receptor type 1 knockout (IL-1R1-/-) mice
Authors
KeywordsHelicobacter pylori
Interleukin-1b
E-cadherin
Nitric oxide
Gastric cancer
Inflammation
DNA methylation
Issue Date2013
PublisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/ejca
Citation
European Journal of Cancer, 2013, v. 49 n. 12, p. 2760-2770 How to Cite?
AbstractHelicobacter pylori infection induced interleukin-1b (IL-1b) production and is associated with aberrant DNA methylation and gastric diseases. Here, we investigated the role of IL-1b in H. pylori-induced gastric inflammation and DNA methylation using IL-1 receptor type 1 knockout (IL-1R1_/_) mice, and compared the therapeutic efficacy of antimicrobial therapy with IL-1 receptor antagonist (IL-1ra). IL-1R1_/_ and wild-type (WT) mice were infected with H. pylori for 16, 24 and 32 weeks. Infected WT mice at 24 weeks were given either antimicrobial therapy or IL-1ra. Comparing to the IL-1R1_/_ mice, infected WT mice with functional IL-1b signaling had higher gastritis scores, higher IL-1b and iNOS mRNA expression, higher nitric oxide (NO) production and increased frequency of E-cadherin (Ecad) methylation at all the time points analyzed. IL-1b release was significantly elevated in infected WT mice than normal controls at 16 weeks post-infection (p < 0.005). Treatment of infected mice with antimicrobial therapy and IL-1ra significantly reduced the degree of gastritis (p < 0.005; p < 0.05, respectively), iNOS expression (p < 0.0001; p < 0.01, respectively) and NO production (both p < 0.001) compared with untreated controls. Mice receiving antimicrobial therapy had significantly lower IL-1b expression than untreated controls (p < 0.0001). Both treatments reduced the incidence of E-cad methylation in infected mice compared with controls, however, no statistical significance was observed. There was no significant alteration of total DNA methyltransferase (DNMT) activity. These results demonstrated that IL-1b played a crucial role in H. pylori-induced gastric inflammation and DNA methylation. H. pylori eradication and IL-1ra administration could ameliorate inflammatory stress. © 2013 Elsevier Ltd. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/183758
ISSN
2015 Impact Factor: 6.163
2015 SCImago Journal Rankings: 3.152

 

DC FieldValueLanguage
dc.contributor.authorHuang, FY-
dc.contributor.authorChan, AOO-
dc.contributor.authorLo, RCL-
dc.contributor.authorRashid, A-
dc.contributor.authorWong, DKH-
dc.contributor.authorCho, CH-
dc.contributor.authorLai, CL-
dc.contributor.authorYuen, MF-
dc.date.accessioned2013-06-18T04:12:46Z-
dc.date.available2013-06-18T04:12:46Z-
dc.date.issued2013-
dc.identifier.citationEuropean Journal of Cancer, 2013, v. 49 n. 12, p. 2760-2770-
dc.identifier.issn0959-8049-
dc.identifier.urihttp://hdl.handle.net/10722/183758-
dc.description.abstractHelicobacter pylori infection induced interleukin-1b (IL-1b) production and is associated with aberrant DNA methylation and gastric diseases. Here, we investigated the role of IL-1b in H. pylori-induced gastric inflammation and DNA methylation using IL-1 receptor type 1 knockout (IL-1R1_/_) mice, and compared the therapeutic efficacy of antimicrobial therapy with IL-1 receptor antagonist (IL-1ra). IL-1R1_/_ and wild-type (WT) mice were infected with H. pylori for 16, 24 and 32 weeks. Infected WT mice at 24 weeks were given either antimicrobial therapy or IL-1ra. Comparing to the IL-1R1_/_ mice, infected WT mice with functional IL-1b signaling had higher gastritis scores, higher IL-1b and iNOS mRNA expression, higher nitric oxide (NO) production and increased frequency of E-cadherin (Ecad) methylation at all the time points analyzed. IL-1b release was significantly elevated in infected WT mice than normal controls at 16 weeks post-infection (p < 0.005). Treatment of infected mice with antimicrobial therapy and IL-1ra significantly reduced the degree of gastritis (p < 0.005; p < 0.05, respectively), iNOS expression (p < 0.0001; p < 0.01, respectively) and NO production (both p < 0.001) compared with untreated controls. Mice receiving antimicrobial therapy had significantly lower IL-1b expression than untreated controls (p < 0.0001). Both treatments reduced the incidence of E-cad methylation in infected mice compared with controls, however, no statistical significance was observed. There was no significant alteration of total DNA methyltransferase (DNMT) activity. These results demonstrated that IL-1b played a crucial role in H. pylori-induced gastric inflammation and DNA methylation. H. pylori eradication and IL-1ra administration could ameliorate inflammatory stress. © 2013 Elsevier Ltd. All rights reserved.-
dc.languageeng-
dc.publisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/ejca-
dc.relation.ispartofEuropean Journal of Cancer-
dc.subjectHelicobacter pylori-
dc.subjectInterleukin-1b-
dc.subjectE-cadherin-
dc.subjectNitric oxide-
dc.subjectGastric cancer-
dc.subjectInflammation-
dc.subjectDNA methylation-
dc.subject.meshDNA Methylation - immunology-
dc.subject.meshGastritis/genetics - immunology/prevention & control-
dc.subject.meshHelicobacter Infections/genetics - immunology/microbiology-
dc.subject.meshInterleukin-1beta/genetics - immunology/metabolism-
dc.subject.meshReceptors, Interleukin-1 Type I/genetics - immunology/metabolism-
dc.titleCharacterization of interleukin-1β in Helicobacter pylori-induced gastric inflammation and DNA methylation in interleukin-1 receptor type 1 knockout (IL-1R1-/-) mice-
dc.typeArticle-
dc.identifier.emailHuang, FY: fungyu@hkucc.hku.hk-
dc.identifier.emailChan, AOO: aoochan@hku.hk-
dc.identifier.emailLo, RCL: loregina@hku.hk-
dc.identifier.emailWong, DKH: danywong@hku.hk-
dc.identifier.emailCho, CH: chcho@hku.hk-
dc.identifier.emailLai, CL: hrmelcl@hku.hk-
dc.identifier.emailYuen, MF: mfyuen@hku.hk-
dc.identifier.authorityLo, RCL=rp01359-
dc.identifier.authorityWong, DKH=rp00492-
dc.identifier.authorityLai, CL=rp00314-
dc.identifier.authorityYuen, MF=rp00479-
dc.identifier.doi10.1016/j.ejca.2013.03.031-
dc.identifier.pmid23664095-
dc.identifier.hkuros214875-
dc.identifier.volume49-
dc.identifier.issue12-
dc.identifier.spage2760-
dc.identifier.epage2770-
dc.publisher.placeUnited Kingdom-
dc.customcontrol.immutablesml 150428-

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