Abstract
BACKGROUND: The inflammatory response of macrophages is responsible for sepsis. Long noncoding RNA nuclear enriched abundant transcript 1 (NEAT1) has been reported to be involved in sepsis development. However, its underlying mechanism remains largely unclear. This study aims to investigate the effect of NEAT1 on inflammatory response of macrophages and explore the regulatory network of NEAT1/microRNA-17-5p (miR-17-5p)/Toll-like receptor 4 (TLR4). METHODS: The serum samples of 68 sepsis patients and 32 heathy controls were collected. THP-1 macrophages were treated with lipopolysaccharide (LPS) to induce inflammatory injury model of sepsis. The expressions of NEAT1, miR-17-5p and TLR4 were measured by quantitative real-time polymerase chain reaction or western blot. The inflammatory response was investigated by levels of inflammatory cytokines, tumor necrosis factor-alpha (TNF-ɑ), interleukin-1beta (IL-1β) and IL-6 as well as nitric oxide (NO) production. The interaction among NEAT1, miR-17-5p and TLR4 were investigated by bioinformatics analysis, luciferase reporter assay and RNA pull-down. RESULTS: NEAT1 expression was enhanced in patient serum and associated with severity of sepsis. Knockdown of NEAT1 inhibited levels of TNF-ɑ, IL-1β, IL-6 and NO release in LPS-treated macrophages. miR-17-5p is bound to NEAT1 and its abrogation reversed NEAT1 knockdown-mediated inhibition of inflammatory response in LPS-treated macrophages. Overexpression of miR-17-5p weakened LPS-induced inflammatory response. TLR4 as a target of miR-17-5p was regulated by NEAT1 and miR-17-5p. TLR4 res-to ration alleviated silencing NEAT1-induced inflammatory suppression. CONCLUSION: Silence of NEAT1 suppressed LPS-induced inflammatory response of macrophages by mediating miR-17-5p and TLR4, indicating that NEAT1 might be a promising target for sepsis treatment.