Gastroenterology

Gastroenterology

Volume 133, Issue 3, September 2007, Pages 918-925
Gastroenterology

Basic–alimentary tract
Enteric Glial-Derived S100B Protein Stimulates Nitric Oxide Production in Celiac Disease

https://doi.org/10.1053/j.gastro.2007.06.009Get rights and content

Background & Aims: Enteric glia participates to the homeostasis of the gastrointestinal tract. In the central nervous system, increased expression of astroglial-derived S100B protein has been associated with the onset and maintaining of inflammation. The role of enteric glial-derived S100B protein in gastrointestinal inflammation has never been investigated in humans. In this study, we evaluated the expression of S100B and its relationship with nitric oxide production in celiac disease. Methods: Duodenal biopsy specimens from untreated and on gluten-free diet patients with celiac disease and controls were respectively processed for S100B and inducible nitric oxide synthase (iNOS) protein expression and nitrite production. To evaluate the direct involvement of S100B in the inflammation, control biopsy specimens were exposed to exogenous S100B, and iNOS protein expression and nitrite production were measured. We also tested gliadin induction of S100B-dependent inflammation in cultured biopsy specimens deriving from on gluten-free diet patients in the absence or presence of the specific S100B antibody. Results: S100B messenger RNA and protein expression, iNOS protein expression, and nitrite production were significantly increased in untreated patients but not in on gluten-free diet patients vs controls. Addition of S100B to control biopsy specimens resulted in a significant increase of iNOS protein expression and nitrite production. In celiac disease patients but not in controls biopsy specimens, gliadin challenge significantly increased S100B messenger RNA and protein expression, iNOS protein expression, and nitrite production, but these effects were completely inhibited by S100B antibody. Conclusions: Enteric glial-derived S100B is increased in the duodenum of patients with celiac disease and plays a role in nitric oxide production.

Section snippets

Patients

Duodenal biopsy specimens were taken during upper gastrointestinal endoscopy in 22 patients with untreated CD (mean age, 34 years; range, 23–45) serologically diagnosed on the basis of immunoglobulin (Ig)A endomysial, gliadin antibodies, and transglutaminase antibodies positivity and in 21 CD patients on a gluten-free diet (GFD-CD) (mean age, 35 years; range 23–47). Twenty-three subjects (mean age, 45 years; range, 23–67) with dyspeptic symptoms served as controls. We obtained informed consent

S100B mRNA and Protein Expression

In duodenal mucosal biopsy specimens from controls, immunohistochemistry demonstrated that S100B immunopositivity was most readily detectable and confined within the submucosa, with only few EGC processes extended into the mucosa (Figure 1A and 1Ai). In contrast, in CD patients, a stronger and diffuse S100B immunoreactivity was present in the submucosa, together with a marked S100B positivity in the mucosa (Figure 1B and 1Bi). Interestingly, S100B immunostaining decreased in GFD-CD patients, in

Discussion

The traditional assumption is that enteric glia serves as a supportive or nutritive element for enteric neurons. Here, we provide evidence that enteric glia is directly involved in chronic duodenal inflammation occurring in CD and that increased S100B mRNA and protein expression are accompanied with both iNOS protein expression and relative NO release. The few data compelling the role of S100B in the intestine indicate that this protein is exclusively localized in enteroglial cells,12, 13, 14

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    Supported by research funds from the Italian Ministry of University and Research (COFIN Projects No. 2004062155 to G.S. and R.C.).

    The authors thank Dr Pietro Micheli and Dr Pasquale Somma, of the Pathologic Anatomy and Histology Service of “Domenico Cotugno” General Hospital, for their contribution to this work and Dr Rosanna Scala for helping with the preparation of the manuscript.

    Conflict of interest: All authors disclose that there is no conflict of interest.

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