TY - JOUR AU - Núñez, Gabriel AB -

Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that plays an important role in host defense and inflammatory diseases. The maturation and secretion of IL-1β are mediated by caspase-1, a protease that processes pro-IL-1β into biologically active IL-1β. 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-1β 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.

TI - Differential Requirement of P2X7 Receptor and Intracellular K+ for Caspase-1 Activation Induced by Intracellular and Extracellular Bacteria * JF - Journal of Biological Chemistry DO - 10.1074/jbc.m610762200 DA - 2007-06-29 UR - https://www.deepdyve.com/lp/american-society-for-biochemistry-and-molecular-biology/differential-requirement-of-p2x7-receptor-and-intracellular-k-for-PJpBOUU0rF SP - 18810 EP - 18818 VL - 282 IS - 26 DP - DeepDyve ER -