Glucocorticoid regulation of cell survival in normal and cytokine-treated gastric chief cells

Gastric chief cells secrete pepsinogen and are found at the base of gastric glands. Chief cells constitutively express the anti-apoptotic protein Bcl-xL, which may enable them to live longer than other gastric cells. We reveal that the cytokines released as part of the inflammatory response during Helicobacter pylori infection dose-dependently disrupt chief cell monolayer integrity and viability. We also show that glucocorticoids dose-dependently increase expression of Bcl-xL, and hypothesize that this accounts for the ability of glucocorticoids to protect chief cells from cytokine-induced cell death. In addition, we show that glucocorticoids restrict the ability of cytokines to damage chief cell monolayer integrity. Finally, we propose two mechanisms by which cytokines overwhelm the protective ability of glucocorticoids, resulting in chief cell deletion and gastric atrophy during Helicobacter pylori infection.