NDLI: IL-1 Receptor Antagonist Chimeric Protein: Context-Specific and Inflammation-Restricted Activation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Eini, Hadar Lewis, Eli C. Rider, Peleg Azam, Tania Guttman, Ofer Yossef, Rami Carmi, Yaron Dinarello, Charles A.
Description	Author Affiliation: Rider P ( Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel); Carmi Y ( Department of Pathology, School of Medicine, Stanford University, Palo Alto, CA 95305); Yossef R ( The Shraga Segal Department of Microbiology, Immunology and Genetics and The Cancer Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel); Guttman O ( Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel); Eini H ( Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel); Azam T ( University of Colorado at Denver, Aurora, CO 80045); Dinarello CA ( University of Colorado at Denver, Aurora, CO 80045); Lewis EC ( Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel)
Abstract	Both IL-1 and IL-1ß are highly inflammatory cytokines mediating a wide spectrum of diseases. A recombinant form of the naturally occurring IL-1R antagonist (IL-1Ra), which blocks IL-1R1, is broadly used to treat autoimmune and autoinflammatory diseases; however, blocking IL-1 increases the risk of infection. In this study, we describe the development of a novel form of recombinant IL-1Ra, termed chimeric IL-1Ra. This molecule is a fusion of the N-terminal peptide of IL-1ß and IL-1Ra, resulting in inactive IL-1Ra. Because the IL-1ß N-terminal peptide contains several protease sites clustered around the caspase-1 site, local proteases at sites of inflammation can cleave chimeric IL-1Ra and turn IL-1Ra active. We demonstrate that chimeric IL-1Ra reduces IL-1-mediated inflammation in vitro and in vivo. This unique approach limits IL-1 receptor blockade to sites of inflammation, while sparing a multitude of desired IL-1-related activities, including host defense against infections and IL-1-mediated repair.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	4
Volume Number	195
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2015-08-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Interleukin 1 Receptor Antagonist Protein Pharmacology Receptors, Interleukin-1 Antagonists & Inhibitors Recombinant Fusion Proteins Animals Cell Line Inflammation Immunology Metabolism Genetics Interleukin-1beta Chemistry Killer Cells, Natural Drug Effects Lymphocyte Activation Macrophage Activation Macrophages Mice Pancreatic Elastase Peptide Fragments Protein Interaction Domains And Motifs Proteolysis Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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