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.

Autor:	Abdulqadir R; Department of Medicine, Penn State College of Medicine, Hershey Medical Center, Hershey, Pennsylvania. Electronic address: rabdulqadir@pennstatehealth.psu.edu., Al-Sadi R; Department of Medicine, Penn State College of Medicine, Hershey Medical Center, Hershey, Pennsylvania., Haque M; Department of Medicine, Penn State College of Medicine, Hershey Medical Center, Hershey, Pennsylvania., Gupta Y; Department of Medicine, Penn State College of Medicine, Hershey Medical Center, Hershey, Pennsylvania., Rawat M; Department of Medicine, Penn State College of Medicine, Hershey Medical Center, Hershey, Pennsylvania., Ma TY; Department of Medicine, Penn State College of Medicine, Hershey Medical Center, Hershey, Pennsylvania. Electronic address: thomasma@pennstatehealth.psu.edu.
Jazyk:	angličtina
Zdroj:	The American journal of pathology [Am J Pathol] 2024 Sep; Vol. 194 (9), pp. 1664-1683. Date of Electronic Publication: 2024 Jun 15.
DOI:	10.1016/j.ajpath.2024.05.012
Abstrakt:	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. Competing Interests: Disclosure Statement None declared. (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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