Abstract
Background: Previous studies have indicated that Kupffer cells (KCs) are the main regulatory cells for the activation of hepatic stellate cells (HSCs), and caspase-11/NLRP3 inflammasome signaling plays crucial roles in the activation of monocyte-macrophages. Ursolic acid (UA) is a traditional Chinese medicine with antifibrotic effects, but the molecular mechanism underlying these effects is still unclear.Methods: A mouse primary Kupffer cell line in vitro and liver fibrosis mice (including specific gene knockout mice) in vivo were selected as experimental objects. RT-qPCR and Western blotting techniques were utilized to assess the mRNA and protein expression in each group. ELISA and histological analysis were utilized to assess liver injury and collagen deposition.Results: In vitro, caspase-11/NLRP3 inflammasome signaling promoted the activation of Kupffer cells, and UA inhibited the activation of Kupffer cells by caspase-11/NLRP3 inflammasome signaling. In vivo, UA reversed liver damage and fibrosis in fibrotic mice and was related to Kupffer cells; the expression of Caspase-11/NLRP3 inflammasome signaling in Kupffer cells of the UA group was inhibited. Even in the CCl4 group, the liver damage and fibrosis of NLRP3 knockout mice were alleviated, and related experiments also proved that the inhibitory effect of UA on Kupffer cells was related to the activation of the NLRP3 inflammasome.Conclusion: Caspase-11/NLRP3 inflammasome signal transduction is closely related to the activation of Kupffer cells and the occurrence of liver fibrosis. Additionally, caspase-11/NLRP3 inflammasome signaling serves as a new target for UA antifibrosis treatment.
Vitamin C deficiency attenuates liver fibrosis by way of up-regulated peroxisome proliferator-activated receptor-gamma expression in senescence marker protein 30 knockout mice
