Liposomal IL-22 ameliorates liver fibrosis through miR-let7a/STAT3 signaling in mice |
Paper ID : 1060-ISCH |
Authors |
Ayatollah A. El-shorbagy *1, Medhat W Shafaa2, Rasha Salah Elbeltagy2, Rehab E El-Hennamy2, Soad Nady2 1Helwan University 2Helwan University, Faculty of Science |
Abstract |
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 < 0.05) decreased IL-17 level (−33.1%) of healthy splenocytes compared to non-liposomal IL-22. In vivo therapeutic effect of liposomal IL-22 revealed a significant (p < 0.05) decrease in hepatic granuloma index (−22.1%) and levels of TNF-α (−49.2%) and IL-17 (−57.3%), but a marked increase in IL-22 (64.2%) and IgE (196.1%) levels comparing to non-liposomal IL-22. Additionally, liposomal IL-22 treatment increased hepatic expression of STAT3 (21.7 fold change) and let-7a (3.6 fold change) and reduced β-catenin expression (0.6 fold change) compared to healthy mice. Conclusively, liposomal IL-22 seems more effective in the treatment of liver fibrosis resulting from S. mansoni infection than nonsensical IL-22. |
Keywords |
Liposomal IL-22; Liver fibrosis; STAT3; let-7a miRNA; β-catenin. |
Status: Abstract Accepted (Oral Presentation) |