Lipin-1 integrates lipid synthesis with proinflammatory responses during TLR activation in macrophages.
J Immunol
; 193(9): 4614-22, 2014 Nov 01.
Article
in En
| MEDLINE
| ID: mdl-25252959
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.
Full text:
1
Database:
MEDLINE
Main subject:
Phosphatidate Phosphatase
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Nuclear Proteins
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Toll-Like Receptors
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Lipids
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Macrophage Activation
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Macrophages
Limits:
Animals
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Female
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Humans
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Male
Language:
En
Year:
2014
Type:
Article