Introduction: Animal studies indicate that enteric glial cells (EGC) participate to gut homeostasis and are involved in intestinal inflammation. Nonetheless, in humans, it is still unclear if enteroglial activation is directly involved in, or it is an epiphenomenon of inflammation. Objectives: To evaluate the involvement of enteroglial cells in intestinal inflammation and to verify that EGC are able to directly modulate inflammatory responses in human gut. Methods: Rectal biopsies from 30 healthy subjects and human isolated myenteric ganglia from 10 ileum were stimulated with lipopolysaccharides (LPS)+interferon gamma (IFN-c). Enteroglial activation was evaluated by S100B mRNA, protein expression and secretion. In the same experimental conditions, we evaluated LPS/IFNgamma-induced iNOS protein expression and NO production either in the presence or absence of anti-receptor for advanced glycation endproducts (RAGE) antibody. In a second set of experiments, we stimulated mucosal biopsies with exogenous S100B in the presence of anti-RAGE antibody or SB203580 (inhibitor of p38MAPkinase) or TLCK (inhibitor of Nuclear Factor- jB transcription factor) to evaluate iNOS protein expression, NO production, lipid peroxidation and p38MAPkinase activation. Results: Both in rectal biopsies and in human isolated myenteric ganglia, incubation with LPS/IFN-gamma led to a significant increase of S100B mRNA, protein expression and secretion. In parallel, LPS/IFN-gamma enhanced iNOS protein expression and NO production, which were significantly inhibited by anti-RAGE antibody. Exogenous S100B increased iNOS protein expression, NO production and lipid peroxidation through p38MAPkinase/Nuclear Factor-jB activation and via RAGE. Conclusion: We show that EGC are activated by inflammatory stimuli and directly participate to NO production and lipid peroxidation through S100B upregulation in a RAGE-dependent pathway

Enteric glia directly stimulates inflammation induced responses in human intestine.

SARNELLI, GIOVANNI;GROSSO, MICHELA;CUOMO, ROSARIO
2008

Abstract

Introduction: Animal studies indicate that enteric glial cells (EGC) participate to gut homeostasis and are involved in intestinal inflammation. Nonetheless, in humans, it is still unclear if enteroglial activation is directly involved in, or it is an epiphenomenon of inflammation. Objectives: To evaluate the involvement of enteroglial cells in intestinal inflammation and to verify that EGC are able to directly modulate inflammatory responses in human gut. Methods: Rectal biopsies from 30 healthy subjects and human isolated myenteric ganglia from 10 ileum were stimulated with lipopolysaccharides (LPS)+interferon gamma (IFN-c). Enteroglial activation was evaluated by S100B mRNA, protein expression and secretion. In the same experimental conditions, we evaluated LPS/IFNgamma-induced iNOS protein expression and NO production either in the presence or absence of anti-receptor for advanced glycation endproducts (RAGE) antibody. In a second set of experiments, we stimulated mucosal biopsies with exogenous S100B in the presence of anti-RAGE antibody or SB203580 (inhibitor of p38MAPkinase) or TLCK (inhibitor of Nuclear Factor- jB transcription factor) to evaluate iNOS protein expression, NO production, lipid peroxidation and p38MAPkinase activation. Results: Both in rectal biopsies and in human isolated myenteric ganglia, incubation with LPS/IFN-gamma led to a significant increase of S100B mRNA, protein expression and secretion. In parallel, LPS/IFN-gamma enhanced iNOS protein expression and NO production, which were significantly inhibited by anti-RAGE antibody. Exogenous S100B increased iNOS protein expression, NO production and lipid peroxidation through p38MAPkinase/Nuclear Factor-jB activation and via RAGE. Conclusion: We show that EGC are activated by inflammatory stimuli and directly participate to NO production and lipid peroxidation through S100B upregulation in a RAGE-dependent pathway
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/361434
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact