Prebiotic oligosaccharides directly modulate proinflammatory cytokine production in monocytes via activation of TLR4
Article first published online: 23 DEC 2013
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 58, Issue 5, pages 1098–1110, May 2014
How to Cite
Capitán-Cañadas, F., Ortega-González, M., Guadix, E., Zarzuelo, A., Suárez, M. D., de Medina, F. S. and Martínez-Augustin, O. (2014), Prebiotic oligosaccharides directly modulate proinflammatory cytokine production in monocytes via activation of TLR4. Mol. Nutr. Food Res., 58: 1098–1110. doi: 10.1002/mnfr.201300497
- Issue published online: 22 APR 2014
- Article first published online: 23 DEC 2013
- Manuscript Accepted: 12 OCT 2013
- Manuscript Revised: 10 SEP 2013
- Manuscript Received: 10 JUL 2013
- Ministerio de Economía y Competividad. Grant Numbers: SAF2008–01432, AGL2008–04332, SAF2011–22922, SAF2011–22812
- Instituto de Salud Carlos III
- Toll like receptor 4
Prebiotic 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 results
Prebiotics 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.
We conclude that prebiotics may act as TLR4 ligands or as indirect TLR4 modulators to upregulate cytokine secretion in monocytes.