Toll-Like Receptor 2 Activation by beta 2 -%26gt; 1-Fructans Protects Barrier Function of T84 Human Intestinal Epithelial Cells in a Chain Length-Dependent Manner

作者:Vogt Leonie M*; Meyer Diederick; Pullens Gerdie; Faas Marijke M; Venema Koen; Ramasamy Uttara; Schols Henk A; de Vos Paul
来源:Journal of Nutrition, 2014, 144(7): 1002-1008.
DOI:10.3945/jn.114.191643

摘要

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 beta 2 -%26gt; 1-fructan dietary fibers confer protection on intestinal epithelial cell barrier function via Toll-like receptor 2 (TLR2), and we studied whether beta 2 -%26gt; 1-fructan chain-length differences affect this process. T84 human intestinal epithelial cell monolayers were incubated with 4 beta 2 -%26gt; 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 beta 2 -%26gt; 1-fructans, ECIS experiments were repeated using TLR2 blocking antibody. After preincubation of T84 cells with short-chain beta 2 -%26gt; 1-fructans, the decrease in TEER as induced by PMA (62.3 +/- 5.2%, P %26lt; 0.001) was strongly attenuated (15.2 8.8%, P %26lt; 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 beta 2 -%26gt; 1-fructans was substantially inhibited. Stimulation of human embryonic kidney human TLR2 reporter cells with beta 2 -%26gt; 1-fructans induced activation of nuclear factor kappa-light-chain-enhancer of activated B cells, confirming that beta 2 -%26gt; 1-fructans are specific ligands for TLR2. To conclude, beta 2 -%26gt; 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 beta 2 -%26gt; 1-fructan-mediated health effects.

  • 出版日期2014-7