Fig. 7. Genetic or pharmacologic manipulation of ACC1 and ACC2 attenuates LPS-induced peritoneal inflammation but exacerbates bacterial peritonitis in mice.
(A) Experimental schematic of LPS-induced model of systemic inflammation. (B) Survival curves of male flox or ACCΔLysM mice after intraperitoneal LPS administration (n = 16). (C) Peritoneal lavage cytokine levels 6 hours after LPS administration (n = 5 to 6). (D) Plasma cytokine levels 6 hours after LPS administration (n = 5 to 6). (E) Relative mRNA levels in peritoneal cells from flox or ACCΔLysM mice 6 hours after LPS (n = 5 to 6). (F) C57BL/6J mice were injected with LPS (2 mg/kg) and either DMSO control or firsocostat (25 mg/kg), and cytokines and peritoneal cell mRNA expression were measured at 6 hours. (G) Peritoneal lavage cytokine levels 6 hours after LPS (n = 5 to 6). (H) Plasma cytokine levels 6 hours after LPS (n = 5 to 6). (I) Relative mRNA levels in peritoneal cells isolated 6 hours after LPS administration (n = 5 to 6). For (G) to (I), one outlier in the firsocostat treatment group was removed (ROUT Q = 1%). (J) C57BL/6J mice were pretreated with firsocostat (25 mg/kg) before E. coli inoculation [~9 × 106 colony-forming units (CFUs) per mouse] or saline. (K) Survival of mice pretreated with control or firsocostat before E. coli inoculation or saline (saline, n = 3; E. coli, n = 5). (L) Peritoneal lavage of inoculated mice was serially diluted, and bacterial CFUs were estimated (n = 5). Data represented as means ± SEM. Significance determined by one-tailed Welch’s t test (C to E and G to I), Mantel-Cox test (B and K), or one-tailed Mann-Whitney test (L). *P < 0.05 and **P < 0.01. (A, F, J, and L) Created using BioRender.com.