title: Chronic Heavy Alcohol Use is Associated with Upregulated Paneth Cell Antimicrobials in Gastric Mucosa.
abstract: OBJECTIVE
  How alcohol consumption affects the integrity and the defense mechanisms of the mucosa in the upper gastrointestinal tract is largely unknown. We examined the effect of heavy alcohol use on gastric and duodenal Paneth-cell-derived and epithelial antimicrobial peptides (AMPs), cytokines, and the Wnt pathway, an important regulator of epithelial regeneration.
  
  
  METHODS
  In 22 patients with heavy alcohol use and 17 control subjects, biopsies from gastric corpus, antrum, and duodenum were examined for messenger RNA (mRNA) of AMPs, cytokines, and Wnt pathway factors using real-time PCR. The expression of the α-defensin HD5 was analyzed immunohistochemically. The effect of alcohol exposure on Wnt signaling and AMP production was also studied in a gastric cell line using mRNA and reporter gene assays.
  
  
  RESULTS
  Heavy alcohol use was associated with increased expression of Paneth cell HD5 and HD6 mRNA in the antrum, where these products are normally absent (HD5 mRNA in controls vs.
  
  
  METHODS
  2100±900 and 365 500±161 600, HD6 mRNA: 320±130 and 58 300±32 600 copies per 10 ng total RNA, means±s.e.m., P value: 0.022 and 0.011). Upregulated HD5 was independent of intestinal metaplasia that was observed in a minority of patients. No significant differences were found for β-defensins and cytokines (interleukins IL1β, IL6, IL8, IL10). In patients, Wnt pathway factors showed a trend toward higher levels. In vitro, ethanol exposure induced the production of HD5 and HD6 and activation of the Wnt pathway.
  
  
  CONCLUSIONS
  Alcohol exposure can induce gastric Paneth cell AMP expression. This may be linked to Wnt pathway activation, which has an important role in the epithelial regenerative homeostasis.
authors.affiliation: Dr Margarete-Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tübingen, Tübingen, Germany.
authors.forename: M J
authors.initials: MJ
authors.lastname: Ostaff
authors.affiliation: Department of Gastroenterology, Robert Bosch Hospital, Stuttgart, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Schäfer
authors.affiliation: Dr Margarete-Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tübingen, Tübingen, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Courth
authors.affiliation: Dr Margarete-Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tübingen, Tübingen, Germany.
authors.forename: S R D
authors.initials: SR
authors.lastname: Stebe
authors.affiliation: Department of Pathology, Robert Bosch Hospital, Stuttgart, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Ott
authors.affiliation: Department of Gastroenterology, Robert Bosch Hospital, Stuttgart, Germany.
authors.forename: E F
authors.initials: EF
authors.lastname: Stange
authors.affiliation: Department of Internal Medicine 1, University of Tübingen, Tübingen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Wehkamp