DNA Hypermethylation Downregulates Telomerase Reverse Transcriptase (TERT) during H. pylori-Induced Chronic Inflammation

Figure 3

H. pylori infection decreases mTERT expression in the gastric mucosa of C57BL/6 mice, in the presence of large B lymphocyte aggregates. (a, d) H&E staining and immunostaining of B (b, e) and T (c, f) lymphocytes in gastric sections in infected mice, 12 months after H. pylori SS1 infection (d, e, f) and in control mice (a, b, c). Inflammatory infiltrates were observed in the stomach of infected mice, in the lamina propria and submucosa (c). High number of B lymphocytes (e) and a low number of T lymphocytes (f) were present in the inflammatory cell infiltrates in the infected gastric submucosa (e) compared to uninfected (b and c, respectively). Sections of the stomach from the uninfected mice were negative for both B (b) and T (c) lymphocyte staining. Original magnification ×4, bar: 250 μm (a, b, c), and ×10, bar: 100 μm (d, e, f). (b) mTERT gene expression in gastric tissues of H. pylori SS1-infected mice at 12 and 18 months after infection quantified by real-time qPCR (Taqman). Results are expressed as means ± SD of three independent experiments (infected versus uninfected ; ). (c) TERT immunolabeling in gastric tissue sections from uninfected mice (a, c) and H. pylori SS1-infected (b, d) after 12 (a, b) and 18 (c, d) months. Lower TERT staining is observed in the gastric mucosa in the area of the inflammatory B lymphocyte infiltrates in infected samples. Original magnification: ×10, bar: 100 μm (a, b), and ×4, bar: 250 μm (c, d). (d) Number of TERT-positive cells/mm² mucosal area in gastric tissue sections of uninfected and infected samples at 12 and 18 months. Results are expressed as mean ± SD (infected versus uninfected ) according to Mann–Whitney analysis. (e) Inverse correlation between the number of TERT-positive cells/mm² mucosal area and the total score grading inflammatory lesions in uninfected (white symbols) and infected mice (black symbol), indicating that TERT level decreases with the exacerbation of gastric inflammation. Each symbol represents one mouse.

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