ABSTRACT
In recent years, liver fibrosis has become a hotspot in the field of liver diseases. MicroRNA(miRNA)-mediated Nod-like receptor pyrin domain containing 3(NLRP3) inflammasome activation is pivotal in the pathogenesis of liver fibrosis. The present study mainly discussed the role of miRNA-mediated NLRP3 inflammasome activation in the pathogenesis of liver fibrosis. Different miRNA molecules regulated liver fibrosis by mediating NLRP3 inflammasome activation, including miRNA-350-3 p(miR-350-3 p)/interleukin-6(IL-6)-mediated signal transducer and activator of transcription 3(STAT3)/c-myc signaling pathway, miR-148 a-induced autophagy and apoptosis of hepatic stellate cells via hedgehog signaling pathway, miR-155-mediated NLRP3 inflammasome by the negative feedback of the suppressor of cytokine signaling-1(SOCS-1), miR-181 a-mediated downstream NLRP3 inflammatory pathway activation through mitogen-activated protein kinase kinase(MEK)/extracellular signal-regulated kinase(ERK)/nuclear transcription factor κB(NF-κB) inflammatory pathway, miR-21-promoted expression of NF-κB and NLRP3 of RAW264.7 cells in mice by inhibiting tumor necrosis factor-α inducible protein 3(A20), and miR-20 b-promoted expression of IL-1ß and IL-18 by activating NLRP3 signaling pathway. Additionally, the anti-liver fibrosis mechanism of different active components in Chinese medicines(such as Curcumae Rhizoma, Glycyrrhizae Radix et Rhizoma, Aurantii Fructus, Polygoni Cuspidati Rhizoma et Radix, Moutan Cortex, Paeoniae Radix Alba, Epimedii Folium, and Cinnamomi Cortex) was also explored based on the anti-liver fibrosis effect of miRNA-mediated NLRP3 inflammasome activation.
Subject(s)
Inflammasomes , MicroRNAs , Animals , Hedgehog Proteins , Inflammasomes/genetics , Inflammasomes/metabolism , Interleukin-6 , Liver Cirrhosis/drug therapy , Liver Cirrhosis/genetics , Liver Cirrhosis/metabolism , Medicine, Chinese Traditional , Mice , MicroRNAs/genetics , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Proto-Oncogene Proteins c-myc/metabolism , Signal TransductionABSTRACT
PURPOSE: Carnosol is a phenolic diterpene that has potent antioxidant and anti-inflammatory activities. The purpose of this study was to investigate the preconditioning effects of carnosol on lung injury induced by intestinal ischemia/reperfusion (II/R). METHODS: Rats were divided into control, II/R, and carnosol groups. The II/R model was established by clamping the superior mesenteric artery for 1 h and reperfusion at 2, 4, and 6 h after ischemia. The carnosol group received 3 mg/kg carnosol intraperitoneally 1 h before the operation. The rats were then euthanized, and blood and lung specimens were obtained for analysis. RESULTS: The II/R induced lung injury, characterized by histological changes and significant increasing of bronchoalveolar lavage fluid protein. The activity of lung tissue superoxide was weakened, the tissue myeloperoxidase activity and serum interleukin-6 level increased significantly in II/R groups. A strong positive expression of lung intercellular adhesion molecule-1 (ICAM-1) and nuclear factor kappa B (NF-kappaB) were observed. Pretreatment with carnosol markedly reduced lung injury by increasing the tissue superoxide activity and decreasing the myeloperoxidase activity and interleukin-6 level, which was parallel to the decreased expression of ICAM-1 and NF-kappaB. CONCLUSION: Carnosol was able to ablate lung injury induced by II/R, partly attributed to the inhibition of NF-kappaB activation.