Basic–alimentary tractEnteric Glial-Derived S100B Protein Stimulates Nitric Oxide Production in Celiac Disease
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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Growing role of S100B protein as a putative therapeutic target for neurological- and nonneurological-disorders
2021, Neuroscience and Biobehavioral ReviewsCitation Excerpt :In this respect, S100B has been shown to participate in several processes involved in cellular damage. In particular, at micromolar concentration S100B increases ROS production in neurons, facilitates glutamate-induced neuronal death, induces the perturbation of lipid homeostasis and cell cycle arrest, up-regulates inducible nitric oxide synthase (iNOS), induces the release of nitric oxide (NO) and the NO-dependent death of neurons and glia, activates astrocytes through a pro-inflammatory RAGE-dependent autocrine loop, up-regulates cyclooxygenase-2 (COX-2) expression in microglia, impairs oligodendrogenesis (Huttunen et al., 2000; Bernardini et al., 2010; Bianchi et al., 2010; Esposito et al., 2007; Hu et al., 1996; Petrova et al., 2000; Reali et al., 2012; Shanmugam et al., 2008; Villarreal et al., 2014, 2011), and alters neuronal survival via NFkB signaling (Fig. 4). S100B is able to target a broad range of molecules and is involved in different Ca2+ dependent pathways, including immune system mechanisms.
Effects of Colesevelam on Bowel Symptoms, Biomarkers, and Colonic Mucosal Gene Expression in Patients With Bile Acid Diarrhea in a Randomized Trial
2020, Clinical Gastroenterology and HepatologyCitation Excerpt :Consistent with this hypothesis is our observation of reduced FGF19 in fasting serum samples. Activation of P2RY4 is a downstream effect in BAD, based on our prior studies, and intraluminal sequestration of the BAs likely results in a reduced activation of glial signaling, which is involved in the control of mucosal secretion.22–24 Finally, the increased expression of GPBAR1 with colesevelam is consistent with the prior observation that this receptor (ie, TGR5) is required for colesevelam to induce GLP-1 and alter hepatic glycogen metabolism, and that BAs bound to colesevelam activate a prolonged TGR5-mediated cAMP response.25
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.