| Autor: |
Jones, Nicola L., Day, Andrew S., Jennings, Hilary, Shannon, Patrick T., Galindo-Mata, Esther, Sherman, Philip M. |
| Zdroj: |
Infection and Immunity; May 2002, Vol. 70 Issue: 5 p2591-2597, 7p |
| Abstrakt: |
ABSTRACTRecent evidence suggests that immune-mediated gastric epithelial cell apoptosis through Fas-Fas ligand interactions participates in Helicobacter pyloridisease pathogenesis. To define the role of Fas signaling in vivo, H. pyloristrain SS1 infection in C57BL/6 mice was compared to that in mice deficient in the Fas ligand (gld). gldmice had a degree of gastritis similar to that of C57BL/6 mice after 6 weeks (gastritis score, 5.2 ± 0.6 [mean ± standard error] versus 3.5 ± 0.8) and 12 weeks (4.0 ± 0.7 versus 3.4 ± 0.5) of infection. Bacterial colonization was comparable in each group of mice at 12 weeks of infection (2.1 ± 0.3 versus 1.6 ± 0.3 for gldand C57BL/6, respectively; the difference is not significant). Sixty-seven percent of H. pylori-infected gldmice displayed atrophic changes in the gastric mucosa, compared with 37% of infected C57BL/6 mice, at 12 weeks. In addition, atrophic changes were more severe in H. pylori-infected gldmice (P< 0.05). Splenocytes isolated from H. pylori-infected C57BL/6 mice had a twofold increase in production of the Th1 cytokine gamma interferon (IFN-γ) in response to H. pyloriantigens at both 6 and 12 weeks compared to controls (143 ± 65 versus 69 ±26 pg/ml and 336 ± 73 versus 172 ± 60, respectively). In contrast, there was a lack of detectable IFN-γ in gldmice infected with the bacterium. H. pylori-infected C57BL/6 mice had increased epithelial cell apoptosis compared with sham-infected C57BL/6 mice (35.0 ± 8.9 versus 12.3 ± 6.9; P< 0.05). Epithelial cell apoptosis did not differ between H. pylori-infected and control gldmice (5.2 ± 1.6 versus 6.5 ± 2.9 [not significant]). These data demonstrate that mice with mutations in the Fas ligand develop more severe premalignant mucosal changes in response to infection with H. pyloriin association with both an impaired gastric epithelial cell apoptotic response and IFN-γ production. The Fas death pathway modulates disease pathophysiology following murine infection with H. pylori. Deregulation of the Fas pathway could be involved in the transition from gastritis to gastric cancers during H. pyloriinfection. |
| Databáze: |
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