Prebiotic oligosaccharides directly modulate proinflammatory cytokine production in monocytes via activation of TLR4

Molecular Nutrition and Food Research - Tập 58 Số 5 - Trang 1098-1110 - 2014
Fermín Capitán‐Cañadas1, Mercedes Ortega‐González1, Emilia M. Guadix2, Antonio Zarzuelo3, Marı́a Dolores Suárez1, Fermín Sánchez de Medina3, Olga Martínez‐Augustin1
1Department of Biochemistry and Molecular Biology II, CIBERehd, School of Pharmacy, University of Granada, Granada, Spain
2Department of Chemical Engineering, Faculty of Sciences, University of Granada, Granada, Spain
3Department of Pharmacology, CIBEREHD, School of Pharmacy, University of Granada, Granada, Spain

Tóm tắt

ScopePrebiotic oligosaccharides are currently used in a variety of clinical settings for their effects on intestinal microbiota. Here, we have examined the direct, microbiota independent, effects of prebiotics on monocytes and T lymphocytes in vitro.Methods and resultsPrebiotics generally evoked cytokine secretion (TNF‐α, IL‐6, and IL‐10) by mouse splenocytes but inhibited LPS ‐induced IFN‐γ and IL‐17 release. Inulin was found to enhance LPS‐induced IL‐10 secretion. Splenocytes from TLR4−/− (where TLR is Toll‐like receptor) mice showed a markedly depressed response. Conversely, in both basal and LPS‐stimulated conditions, prebiotic inhibition of IFN‐γ levels was preserved. These results suggested a predominant effect on monocytes via TLR4 ligation and possible inhibition of T cells. Hence, we studied the modulation of primary rat monocytes and T lymphocytes, focusing on fructooligosaccharides (FOS) and inulin. In monocytes, FOS and inulin induced TNF‐α, growth‐regulated oncogene α, and IL‐10, but not IL‐1β release. The NF‐κB inhibitor Bay 11–7082 fully prevented these effects. Pharmacological evidence also indicated a significant involvement of mitogen‐activated protein kinase and phosphatidylinositol‐3‐kinase. There was little effect on T cells. FOS and inulin also generally increased TNF‐α, IL‐1β, and IL‐10, but not IL‐8, in human peripheral blood monocytes.ConclusionWe conclude that prebiotics may act as TLR4 ligands or as indirect TLR4 modulators to upregulate cytokine secretion in monocytes.

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Molecular Nutrition and Food Research

Tập 58 Số 5

1098-1110

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