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Chronic Heavy Alcohol Use is Associated with Upregulated Paneth Cell Antimicrobials in Gastric Mucosa.

Ostaff MJ, Schäfer C, Courth L, Stebe SR, Ott G, Stange EF, Wehkamp J - Clin Transl Gastroenterol (2015)

Bottom Line: 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.No significant differences were found for β-defensins and cytokines (interleukins IL1β, IL6, IL8, IL10).This may be linked to Wnt pathway activation, which has an important role in the epithelial regenerative homeostasis.

View Article: PubMed Central - PubMed

Affiliation: Dr Margarete-Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tübingen, Tübingen, Germany.

ABSTRACT

Objectives: 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.

Patients: 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.

No MeSH data available.


Related in: MedlinePlus

Immunohistochemical staining of HD5 ( × 20 magnification) in biopsies taken from the antrum of controls (a) and patients with heavy alcohol use (b). Specific staining is marked by large arrows. Examples for more unspecific staining are marked by thin arrows.
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fig2: Immunohistochemical staining of HD5 ( × 20 magnification) in biopsies taken from the antrum of controls (a) and patients with heavy alcohol use (b). Specific staining is marked by large arrows. Examples for more unspecific staining are marked by thin arrows.

Mentions: As the results of the mRNA study suggest the increased occurrence of Paneth cells in heavy alcohol use, we aimed at confirming this via immunohistochemistry. These analyses were carried out in antrum biopsies of randomly selected heavy alcohol users and controls (six from each group, all patients with chronic alcohol use were H. pylori negative, one out of six control persons was H. pylori positive). Consistent with the fact that we universally detected low levels of HD5 mRNA in our samples, we found a weak and diffuse staining almost throughout all analyzed mucosal samples (Figure 2). In addition, two out of six patients, who were all negative for H. pylori, showed an even more clear-cut result. They displayed a distinct distribution of HD5-positive cells at the bottom of gastric glands (Figure 3b, lower left and lower middle). In addition to this occurrence of Paneth cell metaplasia, the evaluating pathologist also diagnosed the presence of general intestinal metaplasia (IM) in these two patients.


Chronic Heavy Alcohol Use is Associated with Upregulated Paneth Cell Antimicrobials in Gastric Mucosa.

Ostaff MJ, Schäfer C, Courth L, Stebe SR, Ott G, Stange EF, Wehkamp J - Clin Transl Gastroenterol (2015)

Immunohistochemical staining of HD5 ( × 20 magnification) in biopsies taken from the antrum of controls (a) and patients with heavy alcohol use (b). Specific staining is marked by large arrows. Examples for more unspecific staining are marked by thin arrows.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4816256&req=5

fig2: Immunohistochemical staining of HD5 ( × 20 magnification) in biopsies taken from the antrum of controls (a) and patients with heavy alcohol use (b). Specific staining is marked by large arrows. Examples for more unspecific staining are marked by thin arrows.
Mentions: As the results of the mRNA study suggest the increased occurrence of Paneth cells in heavy alcohol use, we aimed at confirming this via immunohistochemistry. These analyses were carried out in antrum biopsies of randomly selected heavy alcohol users and controls (six from each group, all patients with chronic alcohol use were H. pylori negative, one out of six control persons was H. pylori positive). Consistent with the fact that we universally detected low levels of HD5 mRNA in our samples, we found a weak and diffuse staining almost throughout all analyzed mucosal samples (Figure 2). In addition, two out of six patients, who were all negative for H. pylori, showed an even more clear-cut result. They displayed a distinct distribution of HD5-positive cells at the bottom of gastric glands (Figure 3b, lower left and lower middle). In addition to this occurrence of Paneth cell metaplasia, the evaluating pathologist also diagnosed the presence of general intestinal metaplasia (IM) in these two patients.

Bottom Line: 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.No significant differences were found for β-defensins and cytokines (interleukins IL1β, IL6, IL8, IL10).This may be linked to Wnt pathway activation, which has an important role in the epithelial regenerative homeostasis.

View Article: PubMed Central - PubMed

Affiliation: Dr Margarete-Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tübingen, Tübingen, Germany.

ABSTRACT

Objectives: 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.

Patients: 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.

No MeSH data available.


Related in: MedlinePlus