Lactate Inhibits the Pro-Inflammatory Response and Metabolic Reprogramming in Murine Macrophages in a GPR81-Independent Manner

Lactate is an essential component of carbon metabolism in mammals. Recently, lactate was shown to signal through the G protein coupled receptor 81 (GPR81) and to thus modulate inflammatory processes. This study demonstrates that lactate inhibits pro-inflammatory signaling in a GPR81-independent fash...

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Detalles Bibliográficos
Autores principales: Errea, Agustina, Cayet, Delphine, Marchetti, Philippe, Tang, Cong, Kluza, Jerome, Offermanns, Stefan, Sirard, Jean-Claude, Rumbo, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112849/
https://www.ncbi.nlm.nih.gov/pubmed/27846210
http://dx.doi.org/10.1371/journal.pone.0163694
Descripción
Sumario:Lactate is an essential component of carbon metabolism in mammals. Recently, lactate was shown to signal through the G protein coupled receptor 81 (GPR81) and to thus modulate inflammatory processes. This study demonstrates that lactate inhibits pro-inflammatory signaling in a GPR81-independent fashion. While lipopolysaccharide (LPS) triggered expression of IL-6 and IL-12 p40, and CD40 in bone marrow-derived macrophages, lactate was able to abrogate these responses in a dose dependent manner in Gpr81(-/-) cells as well as in wild type cells. Macrophage activation was impaired when glycolysis was blocked by chemical inhibitors. Remarkably, lactate was found to inhibit LPS-induced glycolysis in wild type as well as in Gpr81(-/-) cells. In conclusion, our study suggests that lactate can induce GPR81-independent metabolic changes that modulate macrophage pro-inflammatory activation.

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