Adenosine is required for sustained inflammasome activation via the A₂A receptor and the HIF-1α pathway.
Copyright policy )Adenosine is required for sustained inflammasome activation via the A₂A receptor and the HIF-1α pathway.
Inflammasome pathways are important in chronic diseases; however, it is not known how the signalling is sustained after initiation. Inflammasome activation is dependent on stimuli such as lipopolysaccharide (LPS) and ATP that provide two distinct signals resulting in rapid production of interleukin (IL)-1β, with the lack of response to repeat stimulation. Here we report that adenosine is a key regulator of inflammasome activity, increasing the duration of the inflammatory response via the A(2A) receptor. Adenosine does not replace signals provided by stimuli such as LPS or ATP but sustains inflammasome activity via a cAMP/PKA/CREB/HIF-1α pathway. In the setting of the lack of IL-1β responses after previous exposure to LPS, adenosine can supersede this tolerogenic state and drive IL-1β production. These data reveal that inflammasome activity is sustained, after initial activation, by A(2A) receptor-mediated signalling.
- New York University School of Medicine United States
- YALE UNIVERSITY
- Yale University United States
- New York University School of Medicine
- New York University United States
Lipopolysaccharides, Male, Adenosine, Receptor, Adenosine A2A, Inflammasomes, Macrophages, Interleukin-1beta, Hypoxia-Inducible Factor 1, alpha Subunit, Cyclic AMP-Dependent Protein Kinases, Mice, Inbred C57BL, Mice, Adenosine Triphosphate, Liver, NLR Family, Pyrin Domain-Containing 3 Protein, Cyclic AMP, Animals, Carrier Proteins, Cyclic AMP Response Element-Binding Protein, Signal Transduction
Lipopolysaccharides, Male, Adenosine, Receptor, Adenosine A2A, Inflammasomes, Macrophages, Interleukin-1beta, Hypoxia-Inducible Factor 1, alpha Subunit, Cyclic AMP-Dependent Protein Kinases, Mice, Inbred C57BL, Mice, Adenosine Triphosphate, Liver, NLR Family, Pyrin Domain-Containing 3 Protein, Cyclic AMP, Animals, Carrier Proteins, Cyclic AMP Response Element-Binding Protein, Signal Transduction
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