Статья

Cutting Edge: NF-κB Activating Pattern Recognition and Cytokine Receptors License NLRP3 Inflammasome Activation by Regulating NLRP3 Expression

Franz BauernfeindDepartment of Clinical Chemistry and Pharmacology, University of Bonn , Bonn,Gábor HorváthDepartment of Infectious Diseases and Immunology, University of Massachusetts Medical School , Worcester, MA 01605Andrea StutzDepartment of Infectious Diseases and Immunology, University of Massachusetts Medical School , Worcester, MA 01605Emad S. AlnemriDepartment of Biochemistry and Molecular Biology, Center for Apoptosis Research, Kimmel Cancer Institute, Thomas Jefferson University , Philadelphia, PA 19107Kelly L. MacDonaldDivision of Infectious and Immunological Diseases, Department of Pediatrics, University of British Columbia and British Columbia’s Children’s Hospital , Vancouver, British Columbia,David P. SpeertDivision of Infectious and Immunological Diseases, Department of Pediatrics, University of British Columbia and British Columbia’s Children’s Hospital , Vancouver, British Columbia,Teresa Fernandes‐AlnemriDepartment of Biochemistry and Molecular Biology, Center for Apoptosis Research, Kimmel Cancer Institute, Thomas Jefferson University , Philadelphia, PA 19107Jianghong WuDepartment of Biochemistry and Molecular Biology, Center for Apoptosis Research, Kimmel Cancer Institute, Thomas Jefferson University , Philadelphia, PA 19107Brian G. MonksDepartment of Infectious Diseases and Immunology, University of Massachusetts Medical School , Worcester, MA 01605Katherine A. FitzgeraldDepartment of Infectious Diseases and Immunology, University of Massachusetts Medical School , Worcester, MA 01605Veit HornungDepartment of Clinical Chemistry and Pharmacology, University of Bonn , Bonn,Eicke LatzDepartment of Infectious Diseases and Immunology, University of Massachusetts Medical School , Worcester, MA 01605

2009en

ABI

Аннотация

The IL-1 family cytokines are regulated on transcriptional and posttranscriptional levels. Pattern recognition and cytokine receptors control pro-IL-1beta transcription whereas inflammasomes regulate the proteolytic processing of pro-IL-1beta. The NLRP3 inflammasome, however, assembles in response to extracellular ATP, pore-forming toxins, or crystals only in the presence of proinflammatory stimuli. How the activation of gene transcription by signaling receptors enables NLRP3 activation remains elusive and controversial. In this study, we show that cell priming through multiple signaling receptors induces NLRP3 expression, which we identified to be a critical checkpoint for NLRP3 activation. Signals provided by NF-kappaB activators are necessary but not sufficient for NLRP3 activation, and a second stimulus such as ATP or crystal-induced damage is required for NLRP3 activation.

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Идентификаторы

DOI: 10.4049/jimmunol.0901363

Цитирования и источники

Цитирований: 2Использованных источников: 0

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