Liposomal IL-22 ameliorates liver fibrosis through miR-let7a/STAT3 signaling in mice

• Published in: International immunopharmacology 2023-11, Vol.124 (Pt B), p.111015-111015, Article 111015
• Main Authors: El-Shorbagy, Ayatollah A., Shafaa, Medhat W., Salah Elbeltagy, Rasha, El-Hennamy, Rehab E., Nady, Soad
• Format: Article
• Language: English
• Subjects: Animals; beta Catenin; Granuloma - pathology; Immunoglobulin E; Interleukin-17; Interleukin-22; let-7a miRNA; Liposomal IL-22; Liposomes - therapeutic use; Liver - pathology; Liver Cirrhosis - drug therapy; Liver Cirrhosis - pathology; Liver fibrosis; Mice; MicroRNAs - genetics; STAT3; Tumor Necrosis Factor-alpha - genetics; β-catenin
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2023.111015

•Drug delivery by liposomes helps the drug reach the target sites.•Liposomal IL-22 has a more therapeutic effect than non-liposomal IL-22.•IL-22/STAT3 control liver fibrosis by modulating expression of let-7a and β-catenin.•Liposomal drugs help in developing more effective therapy for liver fibrosis. The therapeutic effect of liposomal IL-22 versus non-liposomal IL-22 on liver fibrosis was investigated. IL-22 (5 µg/ml) was incorporated into negative charged liposomes. Schistosoma mansoni infected mice were treated with liposomal IL-22 for either 7 or 14 days before decapitation. Liver and spleen were removed and splenocytes were isolated for in vitro investigations. TNF-α, IL-17, IL-22 and IgE levels were assessed. Hepatic granulomas were counted, granuloma index and its developmental stages were calculated. Hepatic expressions of STAT3, β-catenin and let-7a miRNA were evaluated. Liposomal IL-22 size was clustered around 425.9 ± 58.0 nm with negative zeta potential (−18.8 ± 1.3 mV). After 14 days, 65.5% of IL-22 was released from liposomal IL-22 as was gradually observed in vitro. Liposomal IL-22 significantly (p