title: Lactate Inhibits the Pro-Inflammatory Response and Metabolic Reprogramming in Murine Macrophages in a GPR81-Independent Manner.
abstract: 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.
authors.affiliation: Instituto de Estudios Inmunológicos y Fisiopatológicos-CONICET- Nacional Universtity of La Plata, 1900, La Plata, Argentina.
authors.forename: Agustina
authors.initials: A
authors.lastname: Errea
authors.affiliation: Institut Pasteur de Lille, Inserm, CNRS, Univ. Lille, CHU Lille, U1019-UMR8204-CIIL-Center for Infection and Immunity of Lille, F-59000, Lille, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Cayet
authors.affiliation: Univ. Lille, Inserm, CHU Lille, UMR-S 1172-JPArc-Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, F-59000, Lille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Marchetti
authors.affiliation: Department of Pharmacology, Max Planck Institute for Heart and Lung Research, D-61231, Bad Nauheim, Germany.
authors.forename: Cong
authors.initials: C
authors.lastname: Tang
authors.affiliation: Univ. Lille, Inserm, CHU Lille, UMR-S 1172-JPArc-Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, F-59000, Lille, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Kluza
authors.affiliation: Department of Pharmacology, Max Planck Institute for Heart and Lung Research, D-61231, Bad Nauheim, Germany.|Medical Faculty, J.W. Goethe University, D-60590, Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Offermanns
authors.affiliation: Institut Pasteur de Lille, Inserm, CNRS, Univ. Lille, CHU Lille, U1019-UMR8204-CIIL-Center for Infection and Immunity of Lille, F-59000, Lille, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Sirard
authors.affiliation: Instituto de Estudios Inmunológicos y Fisiopatológicos-CONICET- Nacional Universtity of La Plata, 1900, La Plata, Argentina.
authors.forename: Martin
authors.initials: M
authors.lastname: Rumbo
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D065150:Cellular Reprogramming / Q000187:drug effects; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D006019:Glycolysis / Q000187:drug effects; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D019344:Lactic Acid / Q000494:pharmacology*; D008070:Lipopolysaccharides; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008810:Mice, Inbred C57BL; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: C529424:Hcar1 protein, mouse; D008070:Lipopolysaccharides; D043562:Receptors, G-Protein-Coupled; D019344:Lactic Acid