LncRNA NEAT1 promotes inflammatory response in sepsis-induced liver injury via the Let-7a/TLR4 axis

• Published in: International immunopharmacology 2019-10, Vol.75, p.105731-105731, Article 105731
• Main Authors: Zhang, Cui-Cui, Niu, Fang
• Format: Article
• Language: English
• Subjects: Animals; Assaying; Cell culture; Cytokines; Cytokines - immunology; Enzyme-linked immunosorbent assay; Gene expression; HEK293 Cells; Humans; IL-1β; Immunoprecipitation; In vivo methods and tests; Inflammation; Inflammatory; Inflammatory response; Injuries; Interleukin 6; Kupffer cells; Kupffer Cells - immunology; Let-7a; Level (quantity); Lipopolysaccharides; Liver; Liver - immunology; Liver Diseases - etiology; Liver Diseases - genetics; Liver Diseases - immunology; lncRNA NEAT1; Mice; MicroRNAs - immunology; miRNA; RAW 264.7 Cells; RNA, Long Noncoding - immunology; Sepsis; Sepsis - complications; Sepsis - genetics; Sepsis - immunology; Therapeutic applications; TLR4; TLR4 protein; Toll-Like Receptor 4 - immunology; Toll-like receptors; Tumor necrosis factor-α; Western blotting
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2019.105731

Sepsis is a systemic inflammatory response that can lead to organ dysfunction and/or circulatory disorders in severe cases. The dysregulated inflammatory response plays a pivotal role in sepsis-induced liver injury. A variety of microRNAs and lncRNAs have been shown to be involved in the inflammatory response. However, their role in regulating sepsis-induced liver injury remains to be revealed. Human hepatic tissue and healthy tissue were used for in vivo level detection. And Raw264.7 cells and Kupffer cells were used for in vitro modelling. The relative mRNA expression and the protein levels of TNF-α, IL-6 and IL-1β were detected by q-PCR or by enzyme-linked immunosorbent assay (ELISA), respectively. The binding of lncRNA NEAT1/Let-7a and Let-7a/TLR4 was detected by dual-luciferase reporter assay. RNA Immunoprecipitation (RIP) was used to detect the targeting relationship between lncRNA NEAT1 and Let-7a. Western blotting (WB) was used to detect TLR4 expression in different cell models. The overexpression of lncRNA NEAT1 accompanied by Let-7a inhibition and TLR4 activation was found in sepsis-induced liver injury patients. Similarly, LPS stimulation upregulated lncRNA NEAT1 expression, and lncRNA NEAT1 inhibition decreased the levels of inflammatory cytokines in vitro. Let-7a inhibitor treatment as well as TLR4 overexpression rescued the expression of inflammatory cytokines in lncRNA NEAT1-knockdown cells. Moreover, Let-7a interacted with both lncRNA NEAT1 and TLR4. We demonstrate that lncRNA NEAT1 interacts with Let-7a, targeting TLR4 to contribute to the LPS-induced inflammatory response. Our assay can provide a potential therapeutic target for sepsis-induced liver injury. •LncRNA NEAT1was significantly upregulated in sepsis-induced liver injury patients.•Suppression of lncRNA NEAT1 attenuated LPS-induced inflammatory response in vitro.•The lncRNA NEAT1/Let-7a/TLR4 axis was identified.