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ATP-stimulated Release of Interleukin (IL)-1β and IL-18 Requires Priming by Lipopolysaccharide and Is Independent of Caspase-1 Cleavage
- Source :
- Journal of Biological Chemistry. 276:3820-3826
- Publication Year :
- 2001
- Publisher :
- Elsevier BV, 2001.
-
Abstract
- Interleukin (IL)-1beta and IL-18 are structurally similar proteins that require caspase-1 processing for activation. Both proteins are released from the cytosol by unknown pathway(s). To better characterize the release pathway(s) for IL-1beta and IL-18 we evaluated the role of lipopolysaccharide priming, of interleukin-1beta-converting enzyme (ICE) inhibition, of human purinergic receptor (P2X(7)) function, and of signaling pathways in human monocytes induced by ATP. Monocytes rapidly processed and released both IL-1beta and IL-18 after exogenous ATP. Despite its constitutive cytosolic presence, IL-18 required lipopolysaccharide priming for the ATP-induced release. Neither IL-1beta nor IL-18 release was prevented by ICE inhibition, and IL-18 release was not induced by ICE activation itself. Release of both cytokines was blocked completely by a P2X7 receptor antagonist, oxidized ATP, and partially by an antibody to P2X(7) receptor. In evaluating the signaling components involved in the ATP effect, we identified that the protein-tyrosine kinase inhibitor, AG126, produced a profound inhibition of both ICE activation as well as release of IL-1beta/IL-18. Taken together, these results suggest that, although synthesis of IL-1beta and IL-18 differ, ATP-mediated release of both cytokines requires a priming step but not proteolytically functional caspase-1.
- Subjects :
- Lipopolysaccharides
Lipopolysaccharide
Caspase 1
MAP Kinase Kinase Kinase 1
Priming (immunology)
Enzyme-Linked Immunosorbent Assay
Protein Serine-Threonine Kinases
Biology
Biochemistry
Monocytes
chemistry.chemical_compound
Adenosine Triphosphate
Humans
Enzyme Inhibitors
Phosphorylation
Molecular Biology
Cells, Cultured
Receptors, Purinergic P2
Kinase
Hydrolysis
Purinergic receptor
Interleukin-18
Interleukin
Cell Biology
Tyrphostins
Caspase Inhibitors
Cell biology
Cytosol
chemistry
Receptors, Purinergic P2X7
Signal transduction
Interleukin-1
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 276
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....cc4dbfb1a6b78cebfcb5998fdbe59781