ATP-stimulated Release of Interleukin (IL)-1β and IL-18 Requires Priming by Lipopolysaccharide and Is Independent of Caspase-1 Cleavage

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Key Points

This study aims to explore the signaling pathways for IL-1β and IL-18 release in human monocytes stimulated by ATP.
Evaluated the role of lipopolysaccharide priming on ATP-induced IL-1β and IL-18 release in human monocytes.
Utilized a P2X7 receptor antagonist, oxidized ATP, and ICE inhibition to assess their effects on cytokine release.
Analyzed the inhibition of protein-tyrosine kinases in the context of cytokine release.
ATP-stimulated IL-1β and IL-18 release required lipopolysaccharide priming but was independent of caspase-1 cleavage.
Complete blocking of cytokine release was observed with the P2X7 antagonist; partial blocking was noted with anti-P2X7 antibody.
Inhibition of protein-tyrosine kinase AG126 profoundly affected both ICE activation and IL-1β/IL-18 release.

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Demonstrates cytokine release pathways in monocytes, indicating a need for lipopolysaccharide priming.

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Mehta et al. (2001) studied this question.

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