inhibits the TNF-α-induced increase in intestinal epithelial tight junction permeability via a TLR-2 and PI3K-dependent inhibition of NF-κB activation.

Background: Defective intestinal epithelial tight junction (TJ), characterized by an increase in intestinal TJ permeability, has been shown to play a critical role in the pathogenesis of inflammatory bowel disease (IBD). Tumor necrosis factor-α (TNF-α) is a key pro-inflammatory cytokine involved in the immunopathology of IBD and has been shown to cause an increase in intestinal epithelial TJ permeability. Although TNF-α antibodies and other biologics have been advanced for use in IBD treatment, these therapies are associated with severe side effects and have limited efficacy, and there is an urgent need for therapies with benign profiles and high therapeutic efficacy.

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.

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.

Role of in Modulating the Intestinal Epithelial Tight Junction Barrier: Current Knowledge and Perspectives.

The intestinal tight junction (TJ) barrier is a crucial defense mechanism that prevents the passage of intestinal content into the intestinal wall, tissue, and systemic circulation. A compromised intestinal TJ barrier has been identified as a significant factor in inflammatory bowel disease (IBD), necrotizing enterocolitis, and other gut-related inflammatory conditions. Recent studies have revealed the importance of the probiotic bacterial strains of in protecting against intestinal inflammation and IBD pathogenesis via the regulation of intestinal TJ barrier function.

Talk about micromanaging! Role of microRNAs in intestinal barrier function.

Defective intestinal tight-junction (TJ) barrier has been implicated in the pathogenesis of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), and other inflammatory conditions of the gut. The role of microRNAs (miRNA's or miR's) has also been demonstrated in the last two decades in the pathogenesis of IBD and in the regulation of intestinal TJ barrier function. MiRNAs are noncoding regulators of gene expression at the posttranscription level that have an essential role in targeting transcripts encoding proteins of intestinal TJs and their regulators.

Pore properties of Orai1 calcium channel dimers and their activation by the STIM1 ER calcium sensor.

Store-operated Ca entry signals are mediated by plasma membrane Orai channels activated through intermembrane coupling with Ca-sensing STIM proteins in the endoplasmic reticulum (ER). The nature of this elaborate Orai-gating mechanism has remained enigmatic. Based on the Orai structure, mammalian Orai1 channels are hexamers comprising three dimeric subunit pairs.

Cross-linking of Orai1 channels by STIM proteins.

The transmembrane docking of endoplasmic reticulum (ER) Ca-sensing STIM proteins with plasma membrane (PM) Orai Ca channels is a critical but poorly understood step in Ca signal generation. STIM1 protein dimers unfold to expose a discrete STIM-Orai activating region (SOAR1) that tethers and activates Orai1 channels within discrete ER-PM junctions. We reveal that each monomer within the SOAR dimer interacts independently with single Orai1 subunits to mediate cross-linking between Orai1 channels.

A Diatom Ferritin Optimized for Iron Oxidation but Not Iron Storage.

Ferritin from the marine pennate diatom Pseudo-nitzschia multiseries (PmFTN) plays a key role in sustaining growth in iron-limited ocean environments. The di-iron catalytic ferroxidase center of PmFTN (sites A and B) has a nearby third iron site (site C) in an arrangement typically observed in prokaryotic ferritins. Here we demonstrate that Glu-44, a site C ligand, and Glu-130, a residue that bridges iron bound at sites B and C, limit the rate of post-oxidation reorganization of iron coordination and the rate at which Fe(3+) exits the ferroxidase center for storage within the mineral core.

Mechanism of ferrous iron binding and oxidation by ferritin from a pennate diatom.

A novel ferritin was recently found in Pseudo-nitzschia multiseries (PmFTN), a marine pennate diatom that plays a major role in global primary production and carbon sequestration into the deep ocean. Crystals of recombinant PmFTN were soaked in iron and zinc solutions, and the structures were solved to 1.65-2.

Fe-haem bound to Escherichia coli bacterioferritin accelerates iron core formation by an electron transfer mechanism.

BFR (bacterioferritin) is an iron storage and detoxification protein that differs from other ferritins by its ability to bind haem cofactors. Haem bound to BFR is believed to be involved in iron release and was previously thought not to play a role in iron core formation. Investigation of the effect of bound haem on formation of the iron core has been enabled in the present work by development of a method for reconstitution of BFR from Escherichia coli with exogenously added haem at elevated temperature in the presence of a relatively high concentration of sodium chloride.