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.
- Errea, A.; Cayet, D.; Marchetti, P.; Tang, C.; Kluza, J.; Offermanns, S.; Sirard, J. C.; Rumbo, M.
Keywords
- Animals
- Bone Marrow Cells/drug effects/metabolism/pathology
- Cellular Reprogramming/drug effects
- Extracellular Space/metabolism
- Female
- Glycolysis/drug effects
- Inflammation/*metabolism/pathology
- Lactic Acid/*pharmacology
- Lipopolysaccharides
- Macrophages, Peritoneal/drug effects/*metabolism/*pathology
- Mice, Inbred C57BL
- Receptors, G-Protein-Coupled/*metabolism
