Cutting edge: cyclic polypeptide and aminoglycoside antibiotics trigger IL-1β secretion by activating the NLRP3 inflammasome.

Details

Serval ID
serval:BIB_849E5AFB9646
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cutting edge: cyclic polypeptide and aminoglycoside antibiotics trigger IL-1β secretion by activating the NLRP3 inflammasome.
Journal
Journal of Immunology
Author(s)
Allam R., Darisipudi M.N., Rupanagudi K.V., Lichtnekert J., Tschopp J., Anders H.J.
ISSN
1550-6606 (Electronic)
ISSN-L
0022-1767
Publication state
Published
Issued date
2011
Volume
186
Number
5
Pages
2714-2718
Language
english
Abstract
Clinical use of antibiotics is based on their capacity to inhibit bacterial growth via bacteriostatic or bacteriocidal effects. In this article, we show that the aminoglycoside antibiotic neomycin, the cyclic lipopeptide antibiotic polymyxin B, and the cyclic peptide antibiotics gramicidin and tyrothricin can induce IL-1β secretion in bone marrow dendritic cells and macrophages. LPS priming was required to trigger the transcription and translation of pro-IL-1β but was independent of TNFR or IL-1R signaling. All four antibiotics required the NLRP3 inflammasome, the adaptor ASC, and caspase-1 activation to secrete IL-1β, a process that depended on potassium efflux but was independent of P2X7 receptor. All four antibiotics induced neutrophil influx into the peritoneal cavity of mice, which required NLRP3 only in the case of polymyxin B. Together, certain antibiotics have the potential to directly activate innate immunity of the host.
Keywords
Aminoglycosides/pharmacology, Animals, Anti-Bacterial Agents/pharmacology, Bone Marrow Cells/drug effects, Bone Marrow Cells/immunology, Carrier Proteins/genetics, Carrier Proteins/metabolism, Dendritic Cells/immunology, Dendritic Cells/metabolism, Humans, Inflammasomes/genetics, Inflammasomes/metabolism, Interleukin-1beta/biosynthesis, Interleukin-1beta/secretion, Macrophage Activation/drug effects, Macrophage Activation/immunology, Macrophages, Peritoneal/immunology, Macrophages, Peritoneal/metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Peptides, Cyclic/pharmacology, Peritonitis/immunology, Peritonitis/metabolism, Protein Precursors/biosynthesis, Protein Precursors/secretion, Receptors, Interleukin-1/deficiency, Receptors, Interleukin-1/genetics
Pubmed
Web of science
Open Access
Yes
Create date
02/09/2011 9:00
Last modification date
20/08/2019 14:44
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