Figure 1

Screening of an Il-1β reporter fish reveals drugs that reduce endogenous Il-1β mRNA expression. A: Schematic representation of the drug screening workflow. Briefly, 3 dpf larvae were pre-treated with various compounds for 4 hours, followed by manual injury. Next day, larvae that showed an overall decrease in GFP signal (pre-screening) were fixed, fluorescence was quantified (screening step) and positive compounds were re-tested (validation) and mechanistically tested by qRT-PCR for il-1β mRNA. The numbers of tested compounds after each screening step are depicted in red. B: Representative images of 16-18 hpl drug-treated larvae are shown, including negative (DMSO) and positive control (dexamethasone). C: Quantification of the overall GFP fluorescence signal relative to DMSO-treated control is shown for the validation step. All five compounds elicit a ≥50% drop in the overall GFP signal. Dexamethasone treatment (positive control) induced an approx. 50% decrease in overall GFP signal versus control. D: Three out of five compounds lead to a reduction in the relative il-1β mRNA expression in wild-type larvae (50 treated or control larvae were pooled per measurement). Cimetidine (10 µM) and sildenafil citrate lead to a 40% reduction in il-1β mRNA expression, while bortezomib leads to a 70% reduction. Scale bars: 100 µm