Toll-like receptor 2 activation by beta2-->1-fructans protects barrier function of T84 human intestinal epithelial cells in a chain length-dependent manner

L.M. Vogt, D. Meyer, G. Pullens, M.M. Faas, K. Venema, U. Ramasamy, H.A. Schols, P. Vos

Research output: Contribution to journalArticleAcademicpeer-review

19 Citations (Scopus)

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 beta2-->1-fructan dietary fibers confer protection on intestinal epithelial cell barrier function via Toll-like receptor 2 (TLR2), and we studied whether beta2-->1-fructan chain-length differences affect this process. T84 human intestinal epithelial cell monolayers were incubated with 4 beta2-->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 beta2-->1-fructans, ECIS experiments were repeated using TLR2 blocking antibody. After preincubation of T84 cells with short-chain beta2-->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 beta2-->1-fructans was substantially inhibited. Stimulation of human embryonic kidney human TLR2 reporter cells with beta2-->1-fructans induced activation of nuclear factor kappa-light-chain-enhancer of activated B cells, confirming that beta2-->1-fructans are specific ligands for TLR2. To conclude, beta2-->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 beta2-->1-fructan-mediated health effects.
Original languageEnglish
Pages (from-to)1002-1008
JournalJournal of Nutrition
Volume144
Issue number7
DOIs
Publication statusPublished - 1 Jan 2014

Cite this