miR-1184 regulates inflammatory responses and cell apoptosis by targeting TRADD in an LPS-induced cell model of sepsis

Abstract

MicroRNAs (miRs) have been reported to be potential clinical biomarkers for sepsis. miR-1184 is a multifunctional microRNA that exerts roles in the development of various diseases. However, the role of miR-1184 in children with sepsis remain unknown. In the present study, THP-1 cells were stimulated with 1 µg/ml lipopolysaccharide (LPS) for 24 h to establish an in vitro sepsis model. Reverse transcription-quantitative PCR was used to evaluate the expression of miR-1184 in clinical specimens, and of IL-6, TNF-α, IL-1β, miR-1184 and TNF receptor type 1-associated DEATH domain protein (TRADD) in cells with and without LPS treatment. Cell apoptosis was assessed using flow cytometry. Binding between miR-1184 and TRADD was predicted using bioinformatics software, and a luciferase reporter assay was performed to verify the interaction between miR-1184 and TRADD in LPS-induced THP-1 cells. In addition, western blot analysis was performed to detect TRADD and proteins associated with the NF-κB pathway. The results showed that miR-1184 was downregulated in the blood of children with sepsis and LPS-induced THP-1 cells. Overexpression of miR-1184 alleviated the LPS-induced production of inflammatory cytokines and cell apoptosis. Moreover, TRADD was verified to be a direct target of miR-1184. Upregulation of TRADD reversed the effects of miR-1184 on the LPS-induced inflammatory response and apoptosis of THP-1 cells. Furthermore, the NF-κB pathway was shown to be associated with the regulatory role of miR-1184 in sepsis. The present study provides evidence that miR-1184 exerts inhibitory effects on inflammatory responses and apoptosis in sepsis by targeting TRADD, which suggests that miR-1184 may be a novel potential target for the therapy of children with sepsis.