| First Author | Franchi L | Year | 2007 |
| Journal | J Biol Chem | Volume | 282 |
| Issue | 26 | Pages | 18810-8 |
| PubMed ID | 17491021 | Mgi Jnum | J:295920 |
| Mgi Id | MGI:6458871 | Doi | 10.1074/jbc.M610762200 |
| Citation | Franchi L, et al. (2007) Differential requirement of P2X7 receptor and intracellular K+ for caspase-1 activation induced by intracellular and extracellular bacteria. J Biol Chem 282(26):18810-8 |
| abstractText | Interleukin-1beta (IL-1beta) is a pro-inflammatory cytokine that plays an important role in host defense and inflammatory diseases. The maturation and secretion of IL-1beta are mediated by caspase-1, a protease that processes pro-IL-1beta into biologically active IL-1beta. The activity of caspase-1 is controlled by the inflammasome, a multiprotein complex formed by NLR proteins and the adaptor ASC, that induces the activation of caspase-1. The current model proposes that changes in the intracellular concentration of K(+) potentiate caspase-1 activation induced by the recognition of bacterial products. However, the roles of P2X7 receptor and intracellular K(+) in IL-1beta secretion induced by bacterial infection remain unknown. Here we show that, in response to Toll-like receptor agonists such as lipopolysaccharide or infection with extracellular bacteria Staphylococcus aureus and Escherichia coli, efficient caspase-1 activation is only triggered by addition of ATP, a signal that promotes caspase-1 activation through depletion of intracellular K(+) caused by stimulation of the purinergic P2X7 receptor. In contrast, activation of caspase-1 that relies on cytosolic sensing of flagellin or intracellular bacteria did not require ATP stimulation or depletion of cytoplasmic K(+). Consistently, caspase-1 activation induced by intracellular Salmonella or Listeria was unimpaired in macrophages deficient in P2X7 receptor. These results indicate that, unlike caspase-1 induced by Toll-like receptor agonists and ATP, activation of the inflammasome by intracellular bacteria and cytosolic flagellin proceeds normally in the absence of P2X7 receptor-mediated cytoplasmic K(+) perturbations. |
