The role of potassium in inflammasome activation by bacteria.
Details
State: Public
Version: Final published version
Serval ID
serval:BIB_5A09434E0D93
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The role of potassium in inflammasome activation by bacteria.
Journal
Journal of Biological Chemistry
ISSN
1083-351X[electronic], 0021-9258[linking]
Publication state
Published
Issued date
2010
Peer-reviewed
Oui
Volume
285
Number
14
Pages
10508-10518
Language
english
Abstract
Many Gram-negative bacteria possess a type III secretion system (TTSS( paragraph sign)) that can activate the NLRC4 inflammasome, process caspase-1 and lead to secretion of mature IL-1beta. This is dependent on the presence of intracellular flagellin. Previous reports have suggested that this activation is independent of extracellular K(+) and not accompanied by leakage of K(+) from the cell, in contrast to activation of the NLRP3 inflammasome. However, non-flagellated strains of Pseudomonas aeruginosa are able to activate NLRC4, suggesting that formation of a pore in the cell membrane by the TTSS apparatus may be sufficient for inflammasome activation. Thus, we set out to determine if extracellular K(+) influenced P. aeruginosa inflammasome activation. We found that raising extracellular K(+) prevented TTSS NLRC4 activation by the non-flagellated P. aeruginosa strain PA103DeltaUDeltaT at concentrations above 90 mm, higher than those reported to inhibit NLRP3 activation. Infection was accompanied by efflux of K(+) from a minority of cells as determined using the K(+)-sensitive fluorophore PBFI, but no formation of a leaky pore. We obtained exactly the same results following infection with Salmonella typhimurium, previously described as independent of extracellular K(+). The inhibitory effect of raised extracellular K(+) on NLRC4 activation thus reflects a requirement for a decrease in intracellular K(+) for this inflammasome component as well as that described for NLRP3.
Keywords
Animals, Bacterial Proteins/metabolism, Caspase 1/metabolism, Immunoblotting, Inflammation/immunology, Inflammation/metabolism, Interleukin-1beta/metabolism, Mice, Mice, Inbred C57BL, Potassium/metabolism, Pseudomonas Infections/immunology, Pseudomonas Infections/metabolism, Pseudomonas aeruginosa/pathogenicity, Salmonella Infections/immunology, Salmonella Infections/metabolism, Salmonella typhimurium/pathogenicity
Pubmed
Web of science
Open Access
Yes
Create date
07/09/2010 16:41
Last modification date
20/08/2019 15:13