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The Inflammatory Caspases: Key Players in the Host Response to Pathogenic Invasion and Sepsis

Amal Nadiri^1,*, Melissa K. Wolinski^1, and Maya Saleh^2,*

^* Department of Medicine, McGill University, Montreal, Canada; and College of Osteopathic Medicine, Michigan State University, East Lansing, MI 48824

Caspases are cysteinyl-aspartate-specific proteinases known for their role in apoptosis (cell death or apoptotic caspases) and proinflammatory cytokine maturation (inflammatory caspases). The inflammatory caspases were among the first to be discovered, but only recently have the mechanisms leading to their activation and inhibition begun to be elucidated. In this review, we examine the biochemistry, substrates, and function of this unique family of inflammatory proteases, highlight the most recent findings regarding their regulatory mechanisms, and discuss what remains to be understood about their roles in health and disease.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ A.N. and M.K.W. contributed equally to this review.

² Address correspondence and reprint requests to Dr. Maya Saleh, Department of Medicine, McGill University, Montreal, Quebec H3A 1A1, Canada. E-mail address: maya.saleh{at}mcgill.ca

³ Abbreviations used in this paper: CARD, caspase-recruitment domain; PYD, pyrin domain; ICE, IL-1-converting enzyme; LRR, leucine-rich repeat; NLR, NOD-LRR; NAIP, neuronal apoptosis inhibitor protein; NALP, Nacht, CRR, and PyD-containing protein; IPAF, ice protease activating factor; RIP, receptor-interacting protein; ER, endoplasmic reticulum; Crm, cytokine response modifier; SNP, single nucleotide polymorphism.

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