| First Author | Kahlenberg JM | Year | 2005 |
| Journal | J Immunol | Volume | 175 |
| Issue | 11 | Pages | 7611-22 |
| PubMed ID | 16301671 | Mgi Jnum | J:122153 |
| Mgi Id | MGI:3713416 | Doi | 10.4049/jimmunol.175.11.7611 |
| Citation | Kahlenberg JM, et al. (2005) Potentiation of caspase-1 activation by the P2X7 receptor is dependent on TLR signals and requires NF-kappaB-driven protein synthesis. J Immunol 175(11):7611-22 |
| abstractText | The proinflammatory cytokines IL-1beta and IL-18 are inactive until cleaved by the enzyme caspase-1. Stimulation of the P2X7 receptor (P2X7R), an ATP-gated ion channel, triggers rapid activation of caspase-1. In this study we demonstrate that pretreatment of primary and Bac1 murine macrophages with TLR agonists is required for caspase-1 activation by P2X7R but it is not required for activation of the receptor itself. Caspase-1 activation by nigericin, a K+/H+ ionophore, similarly requires LPS priming. This priming by LPS is dependent on protein synthesis, given that cyclohexamide blocks the ability of LPS to prime macrophages for activation of caspase-1 by the P2X7R. This protein synthesis is likely mediated by NF-kappaB, as pretreatment of cells with the proteasome inhibitor MG132, or the IkappaB kinase inhibitor Bay 11-7085 before LPS stimulation blocks the ability of LPS to potentiate the activation of caspase-1 by the P2X7R. Thus, caspase-1 regulation in macrophages requires inflammatory stimuli that signal through the TLRs to up-regulate gene products required for activation of the caspase-1 processing machinery in response to K+-releasing stimuli such as ATP. |
