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- Title
Adenosine and cAMP are potent inhibitors of the NF-κB pathway downstream of immunoreceptors.
- Authors
Minguet, Susana; Huber, Michael; Rosenkranz, Lisa; Schamel, Wolfgang W. A.; Reth, Michael; Brummer, Tilman
- Abstract
Anergic B lymphocytes exert compromised signal transduction towards the activation of NF-κB in response to B cell antigen receptor (BCR) triggering, whereas activation of the ERK pathway appears normal. How this differential down-regulation of the NF-κB pathway is regulated remains still elusive. Here, we demonstrate that stimuli known to enhance 3′,5′-cyclic adenosine monophosphate (cAMP) are capable of selectively suppressing the activation both of NF-κB downstream of the BCR and Toll-like receptor 4 in splenic B lymphocytes and of the high-affinity receptor for IgE in BM-derived mast cells. This suppression is accomplished by blocking phosphorylation and subsequent degradation of the inhibitor of NF-κB. A cAMP-dependent protein kinase (PKA) inhibitor reverses this suppressive effect, indicating that PKA is a downstream effector of cAMP in this process. Importantly, not only drugs that artificially elevate intracellular cAMP levels, but also the nucleoside adenosine, which is known to be a mediator of cellular distress, inhibit the NF-κB pathway. This suggests that adenosine-mediated signals represent an important step in the molecular decision process controlling inflammation versus anergic immune responses. See accompanying Commentary:
- Publication
European Journal of Immunology, 2005, Vol 35, Issue 1, p31
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.200425524