Fig. 9.

Summary of the key findings in this paper. Celastrol (Cel) protects mice from experimental sepsis and endotoxic shock by inhibiting secretion of pro-inflammatory cytokines. Cel directly targets PKM2, HMGB1, and LDHA, as shown using activity-based protein profiling and cellular thermal shift assays. Cel dampens the inflammatory response and glycolysis in LPS-activated macrophages by repressing the activities of PKM2 and HMGB1. LPS lipopolysaccharide, CLP cecal ligation puncture, PEP phosphor-enol-pyruvate, PKM2 pyruvate kinase M2, HMGB1 high mobility group box 1, LDHA lactate dehydrogenase A, IL-1β interleukin-1β, IL-6 interleukin-6, TNF-α tumor necrosis factor-α