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Differential requirement for the activation of the inflammasome for processing and release of IL-1beta in monocytes and macrophages.
- Source :
-
Blood [Blood] 2009 Mar 05; Vol. 113 (10), pp. 2324-35. Date of Electronic Publication: 2008 Dec 22. - Publication Year :
- 2009
-
Abstract
- The processing of pro-interleukin-1beta depends on activation of caspase-1. Controversy has arisen whether Toll-like receptor (TLR) ligands alone can activate caspase-1 for release of interleukin-1beta (IL-1beta). Here we demonstrate that human blood monocytes release processed IL-1beta after a one-time stimulation with either TLR2 or TLR4 ligands, resulting from constitutively activated caspase-1 and release of endogenous adenosine triphosphate. The constitutive activation of caspase-1 depends on the inflammasome components, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and NALP3, but in monocytes caspase-1 activation is uncoupled from pathogen-associated molecular pattern recognition. In contrast, macrophages are unable to process and release IL-1beta solely by TLR ligands and require a second adenosine triphosphate stimulation. We conclude that IL-1beta production is differentially regulated in monocytes and macrophages, and this reflects their separate functions in host defense and inflammation.
- Subjects :
- Adenosine Triphosphate immunology
Adenosine Triphosphate metabolism
Animals
Blotting, Western
CARD Signaling Adaptor Proteins
CHO Cells
Carrier Proteins immunology
Carrier Proteins metabolism
Caspase 1 immunology
Caspase 1 metabolism
Cricetinae
Cricetulus
Cytoskeletal Proteins immunology
Cytoskeletal Proteins metabolism
Enzyme Activation immunology
Humans
Lipopolysaccharides immunology
Monocytes immunology
NLR Family, Pyrin Domain-Containing 3 Protein
RNA, Small Interfering
Reverse Transcriptase Polymerase Chain Reaction
Inflammation immunology
Interleukin-1beta metabolism
Macrophages immunology
Monocytes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 113
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 19104081
- Full Text :
- https://doi.org/10.1182/blood-2008-03-146720