Title
Toll-like receptor 2 activation by β2→1-fructans protects barrier function of t84 human intestinal epithelial cells in a chain length-dependent manner
Author
Vogt, L.M.
Meyer, D.
Pullens, G.
Faas, M.M.
Venema, K.
Ramasamy, U.
Schols, H.A.
de Vos, P.
Publication year
2014
Abstract
Dietary fiber intake is associated with lower incidence and mortality from disease, but the underlying mechanisms of these protective effects are unclear.We hypothesized that β2→1-fructan dietary fibers confer protection on intestinal epithelial cell barrier function via Toll-like receptor 2 (TLR2), and we studied whether β2→1-fructan chain-length differences affect this process. T84 human intestinal epithelial cell monolayers were incubated with 4 β2→1-fructan formulations of different chain-length compositions and were stimulated with the proinflammatory phorbol 12-myristate 13-acetate (PMA). Transepithelial electrical resistance (TEER) was analyzed by electric cell substrate impedance sensing (ECIS) as a measure for tight junction-mediated barrier function. To confirm TLR2 involvement in barrier modulation by β2→1-fructans, ECIS experiments were repeated using TLR2 blocking antibody. After preincubation of T84 cells with short-chain β2→1-fructans, the decrease in TEER as induced by PMA (62.3 ± 5.2%, P < 0.001) was strongly attenuated (15.2 ± 8.8%, P < 0.01). However, when PMA was applied first, no effect on recovery was observed during addition of the fructans. By blocking TLR2 on the T84 cells, the protective effect of short-chain β2→1-fructans was substantially inhibited. Stimulation of human embryonic kidney human TLR2 reporter cells with β2→1-fructans induced activation of nuclear factor kappa-light-chain-enhancer of activated B cells, confirming that β2→1-fructans are specific ligands for TLR2. To conclude, β2→1-fructans exert time-dependent and chain length-dependent protective effects on the T84 intestinal epithelial cell barrier mediated via TLR2. These results suggest that TLR2 located on intestinal epithelial cells could be a target of β2→1-fructan-mediated health effects. © 2014 American Society for Nutrition.Chemicals/CAS: inulinase, 9025-67-6; phorbol 13 acetate 12 myristate, 16561-29-8; toll like receptor 2, 203811-81-8
Subject
Life
MSB - Microbiology and Systems Biology
ELSS - Earth, Life and Social Sciences
Biomedical Innovation
Biology
Healthy Living
Bocking antibody
Inulinase
Phorbol 13 acetate 12 myristate
Receptor activator of nuclear factor kappa B
Short chain fatty acid
Toll like receptor 2
B lymphocyte
Cell function
Cell interaction
Cell protection
Colon carcinoma
Dietary fiber
Electric cell substrate impedance sensing
Electric resistance
Enzyme activation
Enzyme substrate
Human
Human cell
Impedance
Intestine epithelium cell
Intestine function
Permeability barrier
Regulatory mechanism
Tight junction
Transepithelial electrical resistance
To reference this document use:
http://resolver.tudelft.nl/uuid:015fd3e0-6545-4f0c-98f9-eeab45e9b442
DOI
https://doi.org/10.3945/jn.114.191643
TNO identifier
513427
ISSN
1541-6100
Source
Journal of Nutrition, 144 (7), 1002-1008
Document type
article