title: Effects of stress on mouse β-defensin-3 expression in the upper digestive mucosa.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Environmental Pathology and Research Institute of Salivary Gland Health Medicine, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan. eternal.wish@jichi.ac.jp.
authors.forename: Rie
authors.initials: R
authors.lastname: Kawashima
authors.forename: Tomoko
authors.initials: T
authors.lastname: Shimizu
authors.forename: Masahiro
authors.initials: M
authors.lastname: To
authors.forename: Juri
authors.initials: J
authors.lastname: Saruta
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Jinbu
authors.forename: Mikio
authors.initials: M
authors.lastname: Kusama
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tsukinoki
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005881:Gingiva / Q000187:drug effects / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology; D008297:Male; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D013270:Stomach / Q000187:drug effects; D013312:Stress, Physiological / Q000502:physiology; D013315:Stress, Psychological / Q000378:metabolism*; D023083:beta-Defensins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D005938:Glucocorticoids; D023083:beta-Defensins; C540070:beta-defensin 3, mouse; D003345:Corticosterone
keywords: Antimicrobial peptide; defensin; diabetes mellitus; esophagus; stress