IFN- γ, IL-17A, or zonulin rapidly increase the permeability of the blood-brain and small intestinal epithelial barriers: Relevance for neuro-inflammatory diseases.

IFN-γ, IL-17A, or zonulin rapidly increase the permeability of the blood-brain and small intestinal epithelial barriers: Relevance for neuro-inflammatory diseases. Biochem Biophys Res Commun. 2018 Nov 15;: Authors: Rahman MT, Ghosh C, Hossain M, Linfield D, Rezaee F, Janigro D, Marchi N, van Boxel-Dezaire AHH Abstract Breakdown of the blood-brain barrier (BBB) precedes lesion formation in the brains of multiple sclerosis (MS) patients. Since recent data implicate disruption of the small intestinal epithelial barrier (IEB) in the pathogenesis of MS, we hypothesized that the increased permeability of the BBB and IEB are mechanistically linked. Zonulin, a protein produced by small intestine epithelium, can rapidly increase small intestinal permeability. Zonulin blood levels are elevated in MS, but it is unknown whether zonulin can also disrupt the BBB. Increased production of IL-17A and IFN-γ has been implicated in the pathogenesis of MS, epilepsy, and stroke, and these cytokines impact BBB integrity after 24 h. We here report that primary human brain microvascular endothelial cells expressed the EGFR and PAR2 receptors necessary to respond to zonulin, and that zonulin increased BBB permeability to a 40 kDa dextran tracer within 1 h. Moreover, both IL-17A and IFN-γ also rapidly increased BBB and IEB permeability. By using confocal microscopy, we found that exposure of the IEB to zonulin, IFN-γ, or IL-17A in vitro rapidly m...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research

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Source: Epilepsy Curr - Category: Neurology Authors: Tags: Curr Opin Obstet Gynecol Source Type: research
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Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research
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Source: Japanese Journal of Radiology - Category: Radiology Source Type: research
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Source: Epilepsy Curr - Category: Neurology Authors: Tags: Curr Neuropharmacol Source Type: research
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Source: Physiological Reviews - Category: Physiology Authors: Tags: Physiol Rev Source Type: research
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Source: International Review of Neurobiology - Category: Neuroscience Source Type: research
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Source: Acta Neuropathologica - Category: Neurology Source Type: research
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Source: International Review of Neurobiology - Category: Neuroscience Source Type: research
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