Figure 2. IL-33 deficiency ameliorates experimental fibrosis in vivo.

Il33^−/− or C57BL/6 control mice (n=5/group) were treated with CCL₄ for 4 weeks. (A) Livers were stained for determination of fibrillar collagen depositions with Sirius red and hydroxyproline amounts in livers were determined (*p<0.01). (B) Timp1 mRNA in liver total RNA of CCL₄ treated mice or controls was quantified by qPCR (**p<0.01). (C, D) Il33^−/− or C57BL/6 controls underwent BDL surgery. 16d later mice were sacrificed and livers were analyzed: (C) Sections were stained with Sirius red and hydroxyproline amounts in livers were quantified (*p<0.05), (D) mRNAs of selected fibrosis-associated genes in liver total RNA of BDL mice or controls were quantified by qrtPCR. (E) CD1 mice were infected with ~ 30 S. mansoni cercaria. 3 weeks later mice were HD injected with a liver specific expression construct for the soluble ST2 receptor. 4 weeks later mice were sacrificed. Collagen deposits in livers of mice were determined by Sirius red staining and hydroxyproline quantification. Granulomas were counted in 10 low power fields per slide. (n=5/group; ***p<0.001; *p<0.05). Scale bars 200μm.

(F, G, H) Il33^−/− mice were injected with 5μg of a liver specific expression construct for full-length IL-33 (aa 1-260). (F) IL-33 specific immunostaining demonstrating nuclear IL-33 expression in hepatocytes. (G) Analysis of livers of mice 7d after treatment (H) 7d after HD mice were treated with 1,8 ml/kg CCL₄ or 350 mg/kg TAA. 3d later serum IL-33 concentrations were determined by ELISA. (***p<0.001) Data are representative of at least two different experiments with similar results. Scale bars 200μm or 50μm (IL-33 staining).