Effects of Stress on Mouse β-Defensin-3 Expression in the Upper Digestive Mucosa
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Purpose: Gastrointestinal integrity and immune surveillance are affected by stress. Stress also adversely affects mucosal barrier function. β-defensins constitute an integralcomponent 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 digestivemucosa 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 immunohistochemistryto investigate the effects of stress and glucocorticoid administrationon 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 proteinwas lower in the esophagus of stressed mice than non-stressed mice, consistent with the results of mRNA expression analysis. Systemic glucocorticoid administrationalso downregulated esophageal mouse β-defensin-3 mRNA expression. Conclusion:Our novel findings show that stress decreases mouse β-defensin-3 expressionin 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.
Abstract
Purpose: Gastrointestinal integrity and immune surveillance are affected by stress. Stress also adversely affects mucosal barrier function. β-defensins constitute an integralcomponent 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 digestivemucosa 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 immunohistochemistryto investigate the effects of stress and glucocorticoid administrationon 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 proteinwas lower in the esophagus of stressed mice than non-stressed mice, consistent with the results of mRNA expression analysis. Systemic glucocorticoid administrationalso downregulated esophageal mouse β-defensin-3 mRNA expression. Conclusion:Our novel findings show that stress decreases mouse β-defensin-3 expressionin 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.
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