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TLR agonists stimulate Nlrp3-dependent IL-1β production independently of the purinergic P2X7 receptor in dendritic cells and in vivo.


ABSTRACT: On the basis of studies in mouse macrophages, activation of the nucleotide-binding oligomerization domain-like receptor (NLR) pyrin domain-containing 3 (Nlrp3) inflammasome is thought to require two signals. The first signal is provided by TLR stimulation and triggers the synthesis of the IL-1β precursor and Nlrp3. The second signal can be mediated by stimulation of the purinergic receptor P2X ligand-gated ion channel 7 (P2X7) by millimolar concentrations of ATP. However, these high concentrations of ATP are not found normally in the in vivo extracellular milieu, raising concern about the physiological relevance of the ATP-P2X7 pathway of inflammasome activation. In this article, we show that unlike macrophages, murine bone marrow-derived and splenic dendritic cells (DCs) can secrete subst

SUBMITTER: He Y 

PROVIDER: S-EPMC3531812 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature