Fig. 6.

HDAC7 acts via the PPP metabolite RL5P to prioritize responses to proximal danger signals. (A) IL-1β release from the indicated BMM populations infected with either EC958 (MOI 10) or treated with LPS (100 ng/mL) for 4 h, followed by an additional treatment with nigericin for 1 h. (B) IL-1β release from the indicated BMM populations pretreated with the PPP inhibitors 6-aminonicotinamide (6-AN) (0.5 μM) or polydatin (PD) (0.5 μM) for 1 h, followed by infection with EC958 for 4 h. Additional nigericin treatment for 1 h followed. (C) IL-1β release from BMM knocked down for the indicated genes, treated with LPS (0.5 ng/mL) for 4 h followed by nigericin treatment for 1 h. (D) IL-1β release from BMM retrovirally transduced with indicated constructs, treated with LPS (0.5 ng/mL) for 4 h followed by an additional treatment with nigericin for 1 h. (E–H) IL-1β and TNF release from HMDM and BMM pretreated with the indicated concentrations of ribulose-5-phosphate for 16 h, followed by LPS (10 ng/mL) or infection with EC958 for 4 h. Additional treatment with nigericin for 1 h followed. (I and J) Growth curve analysis (A₆₀₀) of EC958 cultured ± H₂O₂ (0.8 mM) in the presence of the indicated concentrations of RL5P (I) or 6-phosphogluconate (6PG) (J) for 12 h. All graphical data (mean ± SEM, n = 3 to 6) are combined from three to six independent experiments unless otherwise specified and are normalized to the MacBlue (A), Hdac7^+/+ (B), LPS-treated no siRNA control (C), LPS-treated empty vector control (D), or LPS-treated BMMs (F, H). Statistical significance was determined using repeated measure two-way ANOVA followed by Sidak’s, or Dunnett’s multiple comparison test (A–H) (ns, not significant; *P < 0.05; **P < 0.01; ****P < 0.0001).