Curcumin Promotes Apoptosis of Activated Hepatic Stellate Cells by Inhibiting Protein Expression of the MyD88 Pathway.

ABSTRACT

Activation and proliferation of hepatic stellate cells (HSC) play an important role in the progress of liver fibrosis. HSC activation occurs in response to inflammatory cytokines, cellular interactions with immune cells, and morphogenetic signals. The literature hints to a role of the adaptor protein MyD88 in fibrosis. Although curcumin has been shown to exert inhibitory effects on the proliferation of HSC in vitro, its influence on the MyD88 pathway in HSC has remained unclear. Here, we investigated whether curcumin accelerates apoptosis of HSC through the MyD88 pathway. HSC (rat HSC T6) were divided into a control group, MyD88 small interfering RNA (siRNA) group, curcumin group, and curcumin + MyD88 siRNA group. The MyD88 siRNA groups were exposed to siRNA for 48 h. The curcumin groups were cultured in the presence of curcumin for 24 h. Apoptosis was detected by flow cytometry. For Toll-like receptor (TLR) 2 and 4 as well as MyD88 and the dependent factors NF-κB, TNF-α, and IL-1ß, mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR). For MyD88, protein expression was further observed by Western Blot. Both curcumin and MyD88 siRNA inhibited the mRNA expression of MyD88 pathway-related effectors (TLR2, TLR4, NF-κB, TNF-α, IL-1ß) in HSC. Furthermore, both treatments reduced the expression of MyD88 protein in HSC and promoted their apoptosis. These effects were more obvious in the curcumin + MyD88 siRNA group. This study demonstrates that curcumin promotes apoptosis of activated HSC by inhibiting the expression of cytokines related to the MyD88 pathway. It elucidates the possible mechanisms of curcumin in inducing apoptosis of HSC through the MyD88 pathway.