mmu-miR-374b-5p modulated inflammatory factors via downregulation of C/EBP β/NF-κB signaling in Kupffer cells during Echinococcus multilocularis infection

Abstract

Abstract Background Alveolar echinococcosis (AE) is an important infectious disease caused by the metacestode larva of Echinococcus multilocularis (E. multilocularis), seriously threatening global public health security. Kupffer cells (KCs) play important roles in inflammasome. However, its role in hepatic alveolar echinococcosis not yet fully elucidated. Methods In this study, qRT-PCR was used to detect the expression level of miR-374b-5p in KCs. C/EBP β, one of the targets of miR-374b-5p, was identified through luciferase reporter assays and loss-of-function and gains. Critical genes involved in NFκB signaling pathway were analyzed by qRT-PCR and western blot. Results This study reported that miR-374b-5p was significantly up-regulated in KCs during E. multilocularis infection, and further showed that miR-374b-5p was able to bind to the 3'-UTR of the C/EBP β gene and regulated its expression. The expression levels of NF-κBp65 and p-NF-κBp65 and pro-inflammatory factor including iNOS, TNFα, and IL6 was attenuated after overexpression of miR-374b-5p while enhanced after suppression of miR-374b-5p. However, the Arg1 expression level was promoted after overexpression of miR-374b-5p while suppressed after suppression of miR-374b-5p. Additionally, the increased protein levels of NF-κBp65 and p-NF-κBp65 were found in the C/EBP β-overexpressed KCs. Conclusions These results demonstrated that miR-374b-5p probably regulated the expression of inflammatory factors via C/EBP β/NF-κB signaling. This finding is helpful to explore the mechanism of inflammation regulation during E. multilocularis infection.