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Título: | Lipin-1 integrates lipid synthesis with proinflammatory responses during TLR activation in macrophages |
Autor: | Meana, Clara CSIC ORCID; Peña, Lucía CSIC ORCID; Lordén, Gema CSIC; Esquinas, Esperanza CSIC; Guijas, Carlos CSIC ORCID; Valdearcos, Martín CSIC; Balsinde, Jesús CSIC ORCID ; Balboa, María A. CSIC ORCID | Fecha de publicación: | 2014 | Editor: | American Association of Immunologists | Citación: | Journal of Immunology 193(9): 4614-4622 (2014) | Resumen: | Lipin-1 is a Mg2+-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. | Versión del editor: | http://dx.doi.org/10.4049/jimmunol.1400238 | URI: | http://hdl.handle.net/10261/116861 | DOI: | 10.4049/jimmunol.1400238 | Identificadores: | doi: 10.4049/jimmunol.1400238 issn: 0022-1767 e-issn: 1550-6606 |
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TLRActivationRevised.pdf | 238,41 kB | Adobe PDF | Visualizar/Abrir |
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