| First Author | Huang FY | Year | 2013 |
| Journal | Eur J Cancer | Volume | 49 |
| Issue | 12 | Pages | 2760-70 |
| PubMed ID | 23664095 | Mgi Jnum | J:199009 |
| Mgi Id | MGI:5500107 | Doi | 10.1016/j.ejca.2013.03.031 |
| Citation | Huang FY, et al. (2013) Characterization of interleukin-1beta in Helicobacter pylori-induced gastric inflammation and DNA methylation in interleukin-1 receptor type 1 knockout (IL-1R1(-/-)) mice. Eur J Cancer 49(12):2760-70 |
| abstractText | Helicobacter pylori infection induced interleukin-1beta (IL-1beta) production and is associated with aberrant DNA methylation and gastric diseases. Here, we investigated the role of IL-1beta 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 32weeks. Infected WT mice at 24weeks were given either antimicrobial therapy or IL-1ra. Comparing to the IL-1R1(-/-) mice, infected WT mice with functional IL-1beta signaling had higher gastritis scores, higher IL-1beta and iNOS mRNA expression, higher nitric oxide (NO) production and increased frequency of E-cadherin (E-cad) methylation at all the time points analyzed. IL-1beta release was significantly elevated in infected WT mice than normal controls at 16weeks 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-1beta 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-1beta played a crucial role in H. pylori-induced gastric inflammation and DNA methylation. H. pylori eradication and IL-1ra administration could ameliorate inflammatory stress. |
