Enteric Glial-Derived S100B Protein Stimulates Nitric Oxide Production in Celiac Disease

Esposito, Giuseppe; Cirillo, Carla; Sarnelli, Giovanni; Filippis, Daniele De; D’Armiento, Francesco Paolo; Rocco, Alba; Nardone, Gerardo; Petruzzelli, Raffaella; Grosso, Michela; Izzo, Paola; Iuvone, Teresa; Cuomo, Rosario

doi:10.1053/j.gastro.2007.06.009

Cited by 90 publications

(131 citation statements)

References 35 publications

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“…27,28,42 Previous studies have reported increases in EGCderived s100β mRNA, protein expression, and secretion in the duodenum of patients with celiac disease and Crohn's disease, as well as in the rectal mucosa of ulcerative colitis patients. 27,42 The differences in GFAP and s100β functions may explain the opposite effects of oxaliplatin treatment on the expression of these proteins observed in our study. GFAP is typically associated with regeneration, whereas s100β is linked to cell damage and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…28 The gut s100β protein, a small signaling diffusible Ca 2+ /Zn 2+ -binding protein, is specifically expressed by EGCs. 27,42 This protein regulates cytoskeletal structure and function and Ca 2+ homeostasis in the cytoplasm of glial cells. 43 Thus, two antibodies, anti-GFAP and anti-s100β, were utilized in this study to identify EGCs at the levels of the myenteric and submucosal plexi, as well as across the entire ileum wall.…”

Section: Discussionmentioning

confidence: 99%

“…22,25,26 EGCs can proliferate and be activated in response to injury and inflammation. 27,28 Previous studies have shown that in the CNS, astrocytes are sensitive to the platinum drug toxicity 29 and contribute to the development and persistence of chronic pain. 30,31 Glial cell inhibition in the CNS reduces oxaliplatin-induced pain.…”

Section: Research-article2016mentioning

confidence: 99%

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Effects of Oxaliplatin Treatment on the Enteric Glial Cells and Neurons in the Mouse Ileum

Robinson

Stojanovska

Rahman

et al. 2016

J Histochem Cytochem.

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SummaryOxaliplatin, currently used for treatment of colorectal and other cancers, causes severe gastrointestinal side effects, including nausea, vomiting, diarrhea, and constipation that are attributed to mucosal damage. However, delayed onset and long-term persistence of these side effects suggest that damage to the enteric nervous system (ENS) regulating physiological function of the gastrointestinal tract may also occur. The ENS comprises myenteric and submucosal neurons and enteric glial cells (EGCs). This study aimed to investigate the effects of oxaliplatin treatment on enteric neurons and EGCs within the mouse ileum. BALB/c mice received repeated intraperitoneal injections of oxaliplatin (3 mg/kg, 3 injections/week). Tissues were collected 3, 7, 14, and 21 days from the commencement of treatment. Decreases in glial fibrillary acidic protein-immunoreactive (IR) EGCs and protein gene product 9.5/β-Tubulin III-IR neurons as well as increase in s100β-IR EGCs after chronic oxaliplatin administration were observed in both the myenteric and submucosal plexi. Changes in EGCs were further observed in cross-sections of the ileum at day 14 and confirmed by Western blotting. Alterations in EGCs correlated with loss of myenteric and submucosal neurons in the ileum from oxaliplatin-treated mice. These changes to the ENS may contribute to the mechanisms underlying gastrointestinal side effects associated with oxaliplatin treatment. (J Histochem Cytochem 64:530-545, 2016)

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Research-article2016mentioning

confidence: 99%

See 1 more Smart Citation

Effects of Oxaliplatin Treatment on the Enteric Glial Cells and Neurons in the Mouse Ileum

Robinson

Stojanovska

Rahman

et al. 2016

J Histochem Cytochem.

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“…Enteric glial c ells (EGC) release neurotropic fac tors and are ac tivated by inflammatory insults. EGC-derived S100B protein released in astroglial c ells is inc reased in the duodenum of patients with CD, with inc reased S100B messenger RNA and protein expression, inc reased iNOS protein expression, and inc reased nitrite produc tion in treated CD [114] . This does not oc c ur in those CD patients on a GFD, or in non-CD control subjects.…”

Section: Alternatives To a Gluten Free Dietmentioning

confidence: 97%

Recent advances in celiac disease

Freeman

Chopra²,

Clandinin³

et al. 2011

WJG

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Celiac disease now affects about one person in a hundred in Europe and North America. In this review, we consider a number of important and exciting recent developments, such as clinical associations, HLA-DQ2 and HLA-DQ8 predispositions, the concept of potential celiac disease, the use of new imaging/endoscopy techniques, and the development of refractory disease. This review will be of use to all internists, pediatricians and gastroenterologists.

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“…An increase in S-100B protein has also been observed and, together with NF-κB activation, leads to enhanced production of NO. The presence of S-100B in enteric glia has previously been shown to increase inducible NO synthase (iNOS), and S-100B-mediated upregulation of iNOS has been demonstrated in ulcerative colitis and also, interestingly, in celiac disease, where there are marked alterations in mucosal integrity (63)(64)(65). It seems likely that the role of NO is bactericidal; however, rather than being homeostatic, an excessive production of NO through the upregulation of iNOS in enteric glia could lead to a breakdown in barrier function (66).…”

Section: Role Of Enteric Glia In Brain Disordersmentioning

confidence: 99%