TY - JOUR
T1 - Bifidobacterium bifidum Strain BB1 Inhibits Tumor Necrosis Factor-α–Induced Increase in Intestinal Epithelial Tight Junction Permeability via Toll-Like Receptor-2/Toll-Like Receptor-6 Receptor Complex–Dependent Stimulation of Peroxisome Proliferator-Activated Receptor γ and Suppression of NF-κB p65
AU - Abdulqadir, Raz
AU - Al-Sadi, Rana
AU - Haque, Mohammad
AU - Gupta, Yash
AU - Rawat, Manmeet
AU - Ma, Thomas Y.
N1 - Publisher Copyright:
© 2024 American Society for Investigative Pathology
PY - 2024/9
Y1 - 2024/9
N2 - Bifidobacterium bifidum strain BB1 causes a strain-specific enhancement in intestinal epithelial tight junction (TJ) barrier. Tumor necrosis factor (TNF)-α induces an increase in intestinal epithelial TJ permeability and promotes intestinal inflammation. The major purpose of this study was to delineate the protective effect of BB1 against the TNF-α–induced increase in intestinal TJ permeability and to unravel the intracellular mechanisms involved. TNF-α produces an increase in intestinal epithelial TJ permeability in Caco-2 monolayers and in mice. Herein, the addition of BB1 inhibited the TNF-α increase in Caco-2 intestinal TJ permeability and mouse intestinal permeability in a strain-specific manner. BB1 inhibited the TNF-α–induced increase in intestinal TJ permeability by interfering with TNF-α–induced enterocyte NF-κB p50/p65 and myosin light chain kinase (MLCK) gene activation. The BB1 protective effect against the TNF-α–induced increase in intestinal permeability was mediated by toll-like receptor-2/toll-like receptor-6 heterodimer complex activation of peroxisome proliferator-activated receptor γ (PPAR-γ) and PPAR-γ pathway inhibition of TNF-α–induced inhibitory kappa B kinase α (IKK-α) activation, which, in turn, resulted in a step-wise inhibition of NF-κB p50/p65, MLCK gene, MLCK kinase activity, and MLCK-induced opening of the TJ barrier. In conclusion, these studies unraveled novel intracellular mechanisms of BB1 protection against the TNF-α–induced increase in intestinal TJ permeability. The current data show that BB1 protects against the TNF-α–induced increase in intestinal epithelial TJ permeability via a PPAR-γ–dependent inhibition of NF-κB p50/p65 and MLCK gene activation.
AB - Bifidobacterium bifidum strain BB1 causes a strain-specific enhancement in intestinal epithelial tight junction (TJ) barrier. Tumor necrosis factor (TNF)-α induces an increase in intestinal epithelial TJ permeability and promotes intestinal inflammation. The major purpose of this study was to delineate the protective effect of BB1 against the TNF-α–induced increase in intestinal TJ permeability and to unravel the intracellular mechanisms involved. TNF-α produces an increase in intestinal epithelial TJ permeability in Caco-2 monolayers and in mice. Herein, the addition of BB1 inhibited the TNF-α increase in Caco-2 intestinal TJ permeability and mouse intestinal permeability in a strain-specific manner. BB1 inhibited the TNF-α–induced increase in intestinal TJ permeability by interfering with TNF-α–induced enterocyte NF-κB p50/p65 and myosin light chain kinase (MLCK) gene activation. The BB1 protective effect against the TNF-α–induced increase in intestinal permeability was mediated by toll-like receptor-2/toll-like receptor-6 heterodimer complex activation of peroxisome proliferator-activated receptor γ (PPAR-γ) and PPAR-γ pathway inhibition of TNF-α–induced inhibitory kappa B kinase α (IKK-α) activation, which, in turn, resulted in a step-wise inhibition of NF-κB p50/p65, MLCK gene, MLCK kinase activity, and MLCK-induced opening of the TJ barrier. In conclusion, these studies unraveled novel intracellular mechanisms of BB1 protection against the TNF-α–induced increase in intestinal TJ permeability. The current data show that BB1 protects against the TNF-α–induced increase in intestinal epithelial TJ permeability via a PPAR-γ–dependent inhibition of NF-κB p50/p65 and MLCK gene activation.
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U2 - 10.1016/j.ajpath.2024.05.012
DO - 10.1016/j.ajpath.2024.05.012
M3 - Article
C2 - 38885924
AN - SCOPUS:85201482709
SN - 0002-9440
VL - 194
SP - 1664
EP - 1683
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 9
ER -