Tumor Necrosis Factor Alpha and Apoptosis in Helicobacter pylori Related Progressive Gastric Damage: A Possible Mechanism of Immune System Involvement in Epithelial Turnover Regulation

Helicobacter pylori (HP) related inflammation is mediated by tumour necrosis factor alpha (TNFα), which “in vitro” increases epithelial apoptosis in response to infection. In the early stages of HP gastritis, a raised epithelial apoptosis occurs; this phenomenon becomes less evident with progression towards intestinal metaplasia. Aim of our study was to analyze “in vivo” mucosal TNFα in relation to epithelial apoptosis in the progression of HP related histological damage. Antral biopsies from 20 HP positive patients were retrospectively studied: 10 with and 10 without intestinal metaplasia (IM and CG group respectively); samples of 10 dyspeptics with normal HP negative stomach (N) were used as control. The following parameters were evaluated by immunohistochemistry: 85 kDa caspase-cleaved fragment (p85) of human poly (ADP-ribose) polymerase (PARP) labelling index (LI) as marker of apoptosis and TNFα LI in stromal cells as marker of inflammatory response. Both epithelial apoptosis and mucosal TNFα expression were higher in chronic active gastritis compared to intestinal metaplasia and controls (PARP and TNFα LI: CG>IM>N; ANOVA & Student-Neumann-Keuls; p<0.05 and p<0.01, respectively). Pearson' s coefficient showed a significant correlation between PARP and TNFα LI in IM and CG groups. Our data show that mucosal TNFα, similarly to what suggested “in vitro”, may be related “in vivo” to epithelial apoptosis thus suggesting a possible mechanism for immune system involvement in the control of gastric epithelial turnover.

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