Sodium-Dependent Glucose Transporter-1 as a Novel Immunological Player in the Intestinal Mucosa

In this study, we demonstrate the protective effect of the activation of sodium-dependent glucose transporter-1 (SGLT-1) on damages induced by TLR ligands, in intestinal epithelial cells and in a murine model of septic shock. In intestinal epithelial cell lines, glucose inhibited the IL-8/keratinocy...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2008-09, Vol.181 (5), p.3126-3136
Main Authors: Palazzo, Marco, Gariboldi, Silvia, Zanobbio, Laura, Selleri, Silvia, Dusio, Giuseppina F, Mauro, Valentina, Rossini, Anna, Balsari, Andrea, Rumio, Cristiano
Format: Article
Language:English
Subjects:
Animals
Cell Line
Chemokines - antagonists & inhibitors
Glucose - administration & dosage
Glucose - pharmacology
Humans
Inflammation
Interleukin-10 - immunology
Intestinal Mucosa - immunology
Lipopolysaccharides - pharmacology
Mice
NF-kappa B - antagonists & inhibitors
Oligodeoxyribonucleotides - pharmacology
Shock, Septic - chemically induced
Shock, Septic - drug therapy
Shock, Septic - pathology
Sodium-Glucose Transporter 1 - immunology
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Summary:In this study, we demonstrate the protective effect of the activation of sodium-dependent glucose transporter-1 (SGLT-1) on damages induced by TLR ligands, in intestinal epithelial cells and in a murine model of septic shock. In intestinal epithelial cell lines, glucose inhibited the IL-8/keratinocyte-derived chemokine production and the activation of the TLR-related transcription factor NF-kappaB stimulated by LPS or CpG-oligodeoxynucleotide. Oral ingestion of glucose was found to protect 100% of mice from lethal endotoxic shock induced by i.p. LPS administration; protection was only observed when glucose was administered orally, not by i.p. route, suggesting the important role of intestinal epithelial cells in this protection. In addition, we observed that the in vivo protection depends on an increase of anti-inflammatory cytokine IL-10. The cornerstone of the observed immunomodulatory and life-saving effects resides in activation of SGLT-1; in fact, the glucose analog 3-O-methyl-d-gluco-pyranose, which induces the transporter activity, but is not metabolized, exerted the same inhibitory effects as glucose both in vitro and in vivo. Thus, we propose that activated SGLT-1, apart from its classical metabolic function, may be a promising target for inhibition of bacteria-induced inflammatory processes and life-saving treatments, assuming a novel role as an immunological player.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.181.5.3126