NDLI: Lipin-1 integrates lipid synthesis with proinflammatory responses during TLR activation in macrophages.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Guijas, Carlos Meana, Clara Esquinas, Esperanza Peña, Lucía Valdearcos, Martín Balsinde, Jesús Balboa, María A. Lordén, Gema
Description	Country affiliation: Spain Author Affiliation: Meana C ( Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas, Universidad de Valladolid, 47003 Valladolid, Spain); Peña L ( Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas, Universidad de Valladolid, 47003 Valladolid, Spain); Lordén G ( Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas, Universidad de Valladolid, 47003 Valladolid, Spain); Esquinas E ( Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas, Universidad de Valladolid, 47003 Valladolid, Spain); Guijas C ( Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas, Universidad de Valladolid, 47003 Valladolid, Spain); Valdearcos M ( Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas, Universidad de Valladolid, 47003 Valladolid, Spain); Balsinde J ( Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas, Universidad de Valladolid, 47003 Valladolid, Spain); Balboa MA ( Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas, Universidad de Valladolid, 47003 Valladolid, Spain)
Abstract	Lipin-1 is a Mg(2+)-dependent phosphatidic acid phosphatase involved in the de novo synthesis of phospholipids and triglycerides. Using macrophages from lipin-1-deficient animals and human macrophages deficient in the enzyme, we show in this work that this phosphatase acts as a proinflammatory mediator during TLR signaling and during the development of in vivo inflammatory processes. After TLR4 stimulation lipin-1-deficient macrophages showed a decreased production of diacylglycerol and activation of MAPKs and AP-1. Consequently, the generation of proinflammatory cytokines like IL-6, IL-12, IL-23, or enzymes like inducible NO synthase and cyclooxygenase 2, was reduced. In addition, animals lacking lipin-1 had a faster recovery from endotoxin administration concomitant with a reduced production of harmful molecules in spleen and liver. These findings demonstrate an unanticipated role for lipin-1 as a mediator of macrophage proinflammatory activation and support a critical link between lipid biosynthesis and systemic inflammatory responses.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	9
Volume Number	193
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Lipids Biosynthesis Macrophage Activation Immunology Macrophages Metabolism Nuclear Proteins Genetics Phosphatidate Phosphatase Toll-like Receptors Animals Cluster Analysis Cytokines Endotoxins Administration & Dosage Gene Expression Gene Expression Profiling Inflammation Inflammation Mediators Mice Mice, Knockout Deficiency Signal Transduction Agonists Transcriptome Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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