Imperial College London
Alternate

ProfessorRobertGlen

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Chair in Computational Medicine
 
 
 
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Contact

 

+44 (0)20 7594 7912r.glen Website

 
 
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Location

 

362Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@misc{Hoyles:2018,
author = {Hoyles, L and Snelling, T and Umlai, U-K and Nicholson, J and Carding, S and Glen, R and McArthur, S},
title = {Propionate has protective and anti-inflammatory effects on the blood–brain barrier},
type = {Poster},
url = {http://hdl.handle.net/10044/1/62966},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - GEN
AB  - Propionate is a short-chain fatty acid (SCFA) produced by the human gut microbiota from dietary substrates, and is biologically active via the G protein coupled receptors FFAR2 and FFAR3. It is taken up from the gut and reaches systemic circulation in micromolar quantities. The blood–brain barrier (BBB) is the major interface between the circulation and central nervous system. FFAR3 is expressed on the vascular endothelium and a likely target for propionate in the BBB. We hypothesized exposure of the BBB to propionate influences barrier integrity and function.Methods and materialsWe investigated the in vitro effects of a physiologically relevant concentration (1 μM) of propionate upon the human immortalised cerebromicrovascular endothelial cell line hCMEC/D3. FFAR3 was present on these cells. We, therefore, performed an unbiased transcriptomic analysis of confluent hCMEC/D3 monolayers treated or not for 24 h with 1 μM propionate, supported by in vitro validation of key findings and assessment of functional endothelial permeability barrier properties.ResultsPropionate treatment had a significant (PFDR < 0.1) effect on the expression of 1136 genes. It inhibited several inflammation-associated pathways: TLR-specific signalling, NFkappaB signalling, and cytosolic DNA-sensing. Functional validation of these findings confirmed the down-regulation of TLR signalling by propionate, achieved primarily through down-regulation of endothelial CD14 expression. Accordingly, propionate prevented LPS-induced increases in paracellular permeability to 70 kDa FITC-dextran and loss of transendothelial electrical resistance. Propionate activated the NFE2L2 (NRF2)-driven protective response against oxidative stress. Confirming these data, propionate limited free reactive oxygen species induction by the mitochondrial respiratory inhibitor rotenone. ConclusionsOur data strongly suggest the SCFA propionate contributes to maintaining BBB integrity and protecting against inflamm
AU  - Hoyles,L
AU  - Snelling,T
AU  - Umlai,U-K
AU  - Nicholson,J
AU  - Carding,S
AU  - Glen,R
AU  - McArthur,S
PY  - 2018///
TI  - Propionate has protective and anti-inflammatory effects on the blood–brain barrier
UR  - http://hdl.handle.net/10044/1/62966
ER  -
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