RT info:eu-repo/semantics/article
T1 Lipin-1 Integrates Lipid Synthesis with Proinflammatory Responses during TLR Activation in Macrophages
A1 Meana, Clara
A1 Peña, Lucía
A1 Lordén, Gema
A1 Esquinas, Esperanza
A1 Guijas, Carlos
A1 Valdearcos, Martín
A1 Balsinde, Jesús
A1 Balboa, María A
AB 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.
SN 0022-1767
YR 2014
FD 2014
LK https://uvadoc.uva.es/handle/10324/79489
UL https://uvadoc.uva.es/handle/10324/79489
LA spa
NO The Journal of Immunology, Nov 2014, vol. 193, n. 9, p. 4614-22
DS UVaDOC
RD 09-nov-2025