The effect of hepatic stellate cell derived-IL-11 on hepatocyte injury in hepatic fibrosis

This study aimed to elucidate the role of Interleukin-11 (IL-11) in hepatic fibrosis (HF) and its potential as a therapeutic target for HF treatment.We investigated IL-11 expression in patients with varying degrees of liver injury through ELISA and immunohistochemistry. A CCl4-induced HF mouse model was constructed to study IL-11 expression and cell apoptosis using Western blotting (WB) and other techniques. The expression of IL-11 was silenced using rAAV8 in the mouse model. In vitro stimulation of hepatic stellate cells (LX-2) with TGF-β1, and of LO-2 cells with exogenous IL-11, were performed. Cell supernatants of TGF-β1-stimulated LX-2 were used to culture LO-2 cells, with apoptosis monitored via flow cytometry and WB.Increased IL-11 levels were observed in patients and the HF mouse model, with silencing reducing IL-11 expression. In vitro experiments revealed increased endogenous IL-11 in TGF-β1-stimulated LX-2 cells and an increase in apoptotic index, IL11RA, and gp130 in IL-11-stimulated LO-2 cells. Cell apoptosis was reduced in the siRNA/IL11, siRNA/IL11RA, and anti-IL11 groups. WB and immunohistochemistry results showed upregulated p-JNK, p-ERK, and p-P53 expressions in the CCl4-induced HF mouse model and IL-11-treated LO-2 cells.Our findings suggest IL-11 enhances LX-2 cell activation and proliferation, and promotes LO-2 cell apoptosis through JNK/ERK signaling pathways. This suggests that targeting IL-11 secretion may serve as a potential therapeutic strategy for HF, providing a foundation for its clinical application in HF treatment.