Aspartate suppresses Toll-like receptor-4 (TLR4)-mediated inflammasome signaling. A: lipopolysaccharide (LPS) treatment induces aspartate production in mouse peritoneal macrophages as measured in the supernatant by enzymatic assay. B: TLR4 agonist LPS induction of Pro-Il1β expression is significantly and dose dependently suppressed by supplementation with aspartate. Aspartate supplementation at 15 mM significantly suppresses LPS-mediated induction of NOD-like receptor family, pyrin domain containing 3 (Nlrp3, C) and Pro-caspase-1 (D). E: aspartate supplementation at 15 mM suppresses release of IL-1β in the supernatant of peritoneal macrophages in the presence of LPS priming and 5 mM ATP. F: d-Aspartate downregulates LPS-stimulated production of IL-1β in mouse peritoneal macrophages. Aspartate supplementation at 15 mM significantly suppresses LPS-mediated induction of Pro-Il1β (G), Nlrp3 (H), and Pro-caspase-1 (I) in Kupffer cells. J: aspartate supplementation at 15 mM suppresses release of IL-1β into the supernatant of Kupffer cells in the presence of LPS priming and 5 mM ATP. Aspartate supplementation at 15 mM significantly suppresses LPS-mediated induction of Pro-Il1β (K), Nlrp3 (L), and Pro-caspase-1 (M) in human peripheral mononucleocytes. N: aspartate supplementation at 15 mM suppresses release of IL-1β into the supernatant of human peripheral mononucleocytes in the presence of LPS priming and 5 mM ATP. *P < 0.05, **P < 0.01, and ***P < 0.001.