Fig. 6.

Low physiologic concentrations of IL-1β secreted by macrophages induce hepatocellular hepcidin independently of IL-6. A) Hepcidin as well as IL-6 mRNA are significantly induced in Huh7 cells using artificially high IL-1β concentrations (10 ng/ml recombinant IL-1β). B) Under 1% O₂ IL-1β (>0.1 ng/ml) significantly increases hepcidin C) but not IL-6 mRNA expression. CEBPδ mRNA is highly upregulated under 1% O₂ by IL-1β concentrations starting from 0.05 ng/ml. D) Under 1% O₂ IL-1β also significantly increases STAT3 phosphorylation. E) MCHM also significantly induces CEBPδ mRNA expression without affecting IL-6 mRNA in Huh7 cells. Treatment of Huh7 cells with IL-1 receptor antagonist (IL-1RA; Anakinra) or F) co-treatment of macrophages with VAS2870 completely inhibited the effect of MCHM on CEBPδ transcription (###, P < 0.001). Hepcidin, IL-6 and CEBPδ mRNA levels were quantified by RT-PCR and presented as mean mRNA normalized to β2-microglobulin ± SD. Significant differences in relation to the respective controls are marked by asterisks (*, P < 0.05; **, P < 0.01; ***, P < 0.001).