Monocyte-derived immature dendritic cells negatively regulate hepatic stellate cells in vitro by secreting IL-10

The development of liver fibrosis is associated with inflammatory responses resulting from chronic liver disease. Immature dendritic cells (imDCs) play an important role in modulating the inflammatory environment of the liver. This study investigated the effects of imDCs on the regulation of hepatic stellate cells (HSCs) during liver fibrosis. We isolated and induced imDCs from monocytes of healthy volunteers, activated LX-2 cells with TGF-β to establish in vivo liver fibrosis HSCs model, and then set up a cell co-culture system with transwell membranes. imDC surface markers and apoptosis rates of LX-2 cells were detected by flow cytometry. The concentration of IL-10 secreted by imDC was measured through ELISA. The expression of α-SMA in LX-2 after co-culture was examined by qRT‑PCR. Proliferation of LX-2 cells were detected by CCK-8. The western blot was used to illustrate the LX-2 activation-related proteins such as Smad3/7 and TGF-β1. The imDCs co-culture group and the interleukin-10 (IL-10) treatment group had similar results, as they were both able to increase apoptosis, inhibit proliferation, downregulate α-SMA mRNA, and reduce TGF-β1 and Smad3 protein expression in LX-2 cells. Additionally, the Smad7 protein level was increased after treatment with imDC and IL-10. However, the results in the IL-10 antagonist group showed the opposite trend to that of imDCs and IL-10 groups. Thus, these results suggest that imDC secretion of IL-10 negatively regulates activated LX-2 cells, probably via inhibition of the TGF-β1/Smad3 pathway and increased expression of Smad7 protein. This may be a potential therapeutic target for liver fibrosis.