Mechanism of Corilagin interference with IL-13/STAT6 signaling pathways in hepatic alternative activation macrophages in schistosomiasis-induced liver fibrosis in mouse model

Abstract

This study tried to find the mechanism of Corilagin interference with interleukin (IL)-13/signal transducer and activator of transcription (STAT) 6 signaling pathways in IL-13-activated liver alternative activation macrophages in schistosomiasis-induced liver fibrosis in Balb/c mice. As a result, IL-13 in serum and the mRNA expression of IL-13 Receptor α1, IL-4 Receptor α and downstream mediators supressor of cytokine signaling (SOCS) 1, Kruppel-like factor (KLF) 4, peroxisome proliferator-activated receptor (PPAR) δ in the liver tissue were significantly inhibited by Corilagin (P<0.05 or 0.01). The protein expression of IL-13 Receptor α1, IL-4 Receptor α, SOCS1, KLF4, PPARγ, PPARδ and Phospho-STAT6 (P-STAT6) in Corilagin group were also markedly suppressed when compared with the model group (P<0.05 or 0.01). Furthermore, the inhibitory effect was enhanced when the concentration of Corilagin increased (P<0.05). By hematoxylin and eosin (HE) staining, when compared with the model group, the Corilagin group showed smaller granulomas (P<0.05 or 0.01). The area of positive cells and integrated optical density (IOD) of CD68, CD206 and KLF4 was significantly decreased by Corilagin stained by IHC (P<0.05 or 0.01). In conclusion, Corilagin had potential to relieve hepatic fibrosis caused by egg granuloma in Schistosoma japonicum infection by decreasing the expression of molecules associated with IL-13/STAT6 signaling pathway in liver alternative activation macrophages.

Keywords: Corilagin; IL-13; Liver fibrosis; M2 macrophage; Schistosomiasis.