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. 2023 Jan 17;120(4):e2212813120. doi: 10.1073/pnas.2212813120

Fig. 1.

Fig. 1.

HDAC7 discriminates between distal and proximal threats during macrophage activation. (A) Model of immunometabolic control of macrophage responses to distal versus proximal danger signals. (B and C) IL-1β and TNF release from HMDM pretreated with TMP195 (10 μM) for 1 h followed by LPS (100 ng/mL), EC958 (MOI 100), or LPS and latex beads for 4 h. Additional nigericin (5 μg/mL) treatment for 2 h followed, where indicated. (D) Immunoblots for pro- and cleaved-IL-1β in indicated BMM populations treated with either LPS (1 ng/mL) or infected with EC958 (MOI 10) for 4 h, followed by nigericin for 1 h (representative of four independent experiments). (E and F) IL-1β release from the indicated BMM populations treated with either LPS (0.5 ng/mL; Left, E and F), infected with EC958 (MOI 10; E, Right), or LPS-coated latex beads (F, Right) for 4 h, followed by nigericin for 1 h. (G) A heatmap showing the expression patterns of pentose phosphate pathway metabolites (highlighted in red) in lysates from wild-type (Hdac7+/+) and Hdac7−/− BMM infected with EC958 (MOI 100, 30 min and 2 h). * and ** indicate statistical comparison between Hdac7+/+ and Hdac7−/− BMM at 30 min postinfection, and † indicates statistical comparison between Hdac7+/+ and Hdac7−/− BMM at 2 h postinfection. Graphical data (mean ± SEM, n = 3 to 7) are combined from three to seven independent experiments (or donors) performed in experimental duplicate. Data are normalized to the Hdac7+/+ LPS-treated, EC958-infected, or LPS-coated latex beads (E and F). Statistical significance was determined using repeated measure two-way ANOVA followed by Sidak’s multiple comparison test (ns, not significant; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001; †P < 0.05).