Proinflammatory stimuli activates human‐derived enteroglial cells and induces autocrine nitric oxide production

Abstract

Our data provide the first evidence that human EGCs directly respond to pro-inflammatory stimuli by changing their expression profile and by proliferating. The finding that stimulated EGCs are able to produce NO points to a role of this cell population in the scenario of intestinal inflammation.

Enteric Glial Cells: Recent Developments and Future Directions

“…48 LPS in combination with interferon gamma increased EGC proliferation. 44 Consistently, in vivo, intestinal inflammation has been shown to stimulate myenteric EGC proliferation. 49 Increasing evidence suggests that EGCs could directly contribute to the intestinal inflammatory response by producing inflammatory mediators.…”

“…In particular, inflammatory cytokines (IL-1b, tumor necrosis factor a, interferon gamma) or bacterial compounds (lipopolysaccharide [LPS]) can increase GFAP expression or S100b expression and secretion. 41,44,45 Inflammation can also alter the expression of various receptors present on EGCs such as glutamate receptors (mGluR5) 46 or endothelin receptors (ET-1B), 47 thereby suggesting modified EGC functions during inflammation. In addition, inflammatory mediators can also modulate EGC proliferation.…”

Enteroglial-derived S100B protein integrates bacteria-induced Toll-like receptor signalling in human enteric glial cells

“…Primary cultures of EGC were obtained according to the method previously described by our group 17. Briefly, specimens of human small bowel were taken from patients undergoing surgery for colorectal cancer (four men, mean age 57±4 years; four women, mean age 59±6 years).…”

“…After 3–4 weeks, EGC were purified using Dynal-Magnet (Miltenyi Biotec GmbH, Bergisch Gladbach, Germany), according to the manufacturer's instructions and to the method we have previously described 17 19. The separation step with dynabeads was performed twice in order to eliminate residual fibroblasts/smooth muscle cells within the culture.…”

Emerging roles for enteric glia in gastrointestinal disorders

“…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).…”