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

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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.