Figure 6.

The anti-inflammatory effect of eplerenone is due to altered responsivity at the level of the macrophage. (A and B) Transcript abundance (determined by qPCR) of genes encoding the macrophage-specific chemo-attractants ccl2 (A) or cxcl11aa (B) in sham and AMP zebrafish larvae exposed to either eplerenone (1.25 µM) or mifepristone (1.25 µM) (n = 4). (C) Transcript abundance of the gene encoding the pro-inflammatory cytokine interleukin 1β (il1b) and the chemokine receptors ccr2 and cxcr3.2 in FACS-sorted macrophages (n.d., not detectable) (n = 3). (D) Number of mpeg+ macrophages that have migrated to the hindbrain 4 hours after Ccl2 injection at 48 hpf (n = 8-13). (E) Representative images of Tg(mpeg:mCherry) at 48 hpf, treated with either vehicle or eplerenone (1.25 µM) and injected with either PBS or 100 nM of recombinant Ccl2. Bars show the mean ± SEM of 3 individual experiments. Data were analyzed using a 1-way ANOVA (A-C) or a 2-way ANOVA (D). Statistical significance is indicated by *P ≤ .05, ****P ≤ .0001.