Inflammatory caspases and inflammasomes: master switches of inflammation.
Fifteen years have passed since the cloning and characterization of the interleukin-1beta-converting enzyme (ICE/caspase-1), the first identified member of a family of proteases currently known as caspases. Caspase-1 is the prototypical member of a subclass of caspases involved in cytokine maturation termed inflammatory caspases that also include caspase-4 caspase -5, caspase -11 and caspase -12. Efforts to elucidate the molecular mechanisms involved in the activation of these proteases have uncovered an important role for the NLR family members, NALPs, NAIP and IPAF. These proteins promote the assembly of multiprotein complexes termed inflammasomes, which are required for activation of inflammatory caspases. This article will review some evolutionary aspects, biochemical evidences and genetic studies, underlining the role of inflammasomes and inflammatory caspases in innate immunity against pathogens, autoinflammatory syndromes and in the biology of reproduction.
Martinon
F
F
Department of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Epalinges, Switzerland.
Tschopp
J
J
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism; D012098:Reproduction; D018805:Sepsis / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D053583:Interleukin-1beta; D046912:Multiprotein Complexes; D020169:Caspases