SENP3 inhibited PKM2 transcription in a HIF-1α-dependent manner and the PKM2 inhibitor shikonin dampened the LPS-induced macrophage inflammatory response. Notes: BMDMs were isolated from Senp3 fl/fl (n = 6) and Senp3 cKO mice (n = 6) and stimulated with LPS (100 ng/mL) for the indicated time. (A) The mRNA expression of key glycolytic enzymes was analyzed using qRT-PCR. (B) SENP3, HIF-1α, and PKM2 levels were determined using immunoblotting at the indicated time points. (C) Effects of the HIF-1α inhibitor PX-478 and HIF-1α agonist FG-4592 on the PKM2 levels of BMDMs from Senp3 fl/fl and Senp3 cKO mice. (D, E) Cells were treated with the PKM2 inhibitor shikonin, after which the transcription levels of IL-6 and TNF-α were measured using qRT-PCR. The graphs show the means ± SDs, and the data shown in A–E are representative of three independent experiments. Values of p < 0.05 were considered statistically significant, and data marked with a one (*), two (**) and three (***) asterisks indicate p values of <0.05, < 0.01 and <0.001, respectively. SENP3, SUMO-specific peptidase 3; LPS, lipopolysaccharide; IL, interleukin; TNF-α, tumor necrosis factor α; HIF-1α, hypoxia-inducible factor-1α; BMDMs, bone marrow-derived macrophages; PKM2, pyruvate kinase M2.