Effects of Stress on Mouse β-Defensin-3 Expression in the Upper Digestive Mucosa

PURPOSE: Gastrointestinal integrity and immune surveillance are affected by stress. Stress also adversely affects mucosal barrier function. β-defensins constitute an integral component of the innate immune system as antimicrobial peptides, serving as the first line of defense against microbial pathogens at the epithelial surfaces of the upper digestive mucosa. The primary objective of this study was to determine the effects of stress on the expression profile of mouse β-defensin-3 in the upper digestive mucosa of mice with diabetes. MATERIALS AND METHODS: We established a mouse model of restraint stress by using NSY/Hos mice with type 2 diabetes mellitus. We used real-time polymerase chain reaction, in situ hybridization, and immunohistochemistry to investigate the effects of stress and glucocorticoid administration on mouse β-defensin-3 expression in the upper digestive mucosa of the gingiva, esophagus, and stomach. RESULTS: Mouse β-defensin-3 mRNA expression was higher in the esophagus than in the gingiva or stomach (p<0.05). In the esophagus, mouse β-defensin-3 mRNA expression was lower in stressed mice than in non-stressed mice (p<0.05). Furthermore, immunoreactivity to mouse β-defensin-3 protein was lower in the esophagus of stressed mice than non-stressed mice, consistent with the results of mRNA expression analysis. Systemic glucocorticoid administration also downregulated esophageal mouse β-defensin-3 mRNA expression. CONCLUSION: Our novel findings show that stress decreases mouse β-defensin-3 expression in the esophagus of mice with diabetes, possibly due to increased endogenous glucocorticoid production. It appears to be highly likely that stress management may normalize mucosal antimicrobial defenses in patients with diabetes.