期刊
MOLECULAR NUTRITION & FOOD RESEARCH
卷 58, 期 2, 页码 384-393出版社
WILEY-BLACKWELL
DOI: 10.1002/mnfr.201300296
关键词
Cytokines; Intestinal epithelial cells; NF-kappa B; Prebiotic; Toll-like receptor 4
资金
- Ministerio de Ciencia e Innovacion [SAF2008-01432, AGL2008-04332, SAF2011-22922, SAF2011-22812]
- Junta de Andalucia [CTS-6736, CTS164]
- Fundacion Ramon Areces
- Ministerio de Educacion
- Junta de Andalucia
- Instituto de Salud Carlos III
Scope: Prebiotic effects of non absorbable glucids depend mainly on digestion by the colonic microbiota. Our aim was to assess nonprebiotic, direct effects of 4 prebiotics, namely fructooligosaccharides, inulin, galactooligosaccharides, and goat's milk oligosaccharides on intestinal epithelial cells. Methods and results: Prebiotics were tested in intestinal epithelial cell 18 (IEC18), HT29, and Caco-2 cells. Cytokine secretion was measured by ELISA and modulated with pharmacological probes and gene silencing. Prebiotics induced the production of growth-related oncogene, (GRO alpha), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 2 (MIP2) in IEC18 cells, with an efficacy that was 50-80% that of LPS. Prebiotics did not change RANTES expression, which was robustly induced by LPS in IEC18 cells. Cytokine secretion was suppressed by Bay11-7082, an inhibitor of I kappa B-alpha phosphorylation. The response was markedly decreased by Myd88 or TLR4 gene knockdown. Prebiotics also elicited cytokine production in HT29 but not in Caco-2 cells, consistent with reduced and vestigial expression of TLR4 in these cell lines, respectively. Prebiotic-induced MCP-1 secretion was reduced also in colonic explants from TLR4 KO mice compared with the controls. Conclusions: We conclude that prebiotics are TLR4 ligands in intestinal epithelial cells and that this may be a relevant mechanism for their in vivo effects.
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