Abstract

BACKGROUND: Microglia reside in the spinal cord plays a key role in the onset, progression of post-spinal cord injury (SCI) neuroinflammation. Curcumin has been shown to exhibit diverse anti-inflammatory and anti-tumor activities. The aim of this study was to explore the effect of curcumin on the inflammatory response in lipopolysaccharide (LPS)-activated microglia and its mechanism.

MATERIAL AND METHODS: The expression levels of phosphorylated-p65 (p-p65), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IκB kinase β (IKKβ) were examined by western blot assay. MiR-199b-5p expression was detected by quantitative real-time polymerase chain reaction assay. The putative binding sites of miR-199b-5p in IKKβ 3’UTR were predicted by bioinformatics, and direct interaction between miR-199b-5p and IKKβ was verified by dual-luciferase reporter assay and RNA-immunoprecipitation assay.

RESULTS: Curcumin significantly suppressed inflammatory response induced by LPS by inactivation of nuclear factor kappa B (NF-κB) in microglial cells, as reflected by the decreased levels of p-p65, as well as the pro-inflammatory mediators, including inducible nitric oxide synthase (iNOS), TNF-α, and IL-1β. Moreover, curcumin increased the level of miR-199b-5p and decreased IKKβ expression in activated microglial cells. Knockdown of miR-199b-5p or overexpression of IKKβ reversed the inhibitory effect of curcumin on inflammatory response and NF-κB activation. MiR-199b-5p directly targeted IKKβ and suppressed its expression. Silencing of IKKβ abolished miR-199b-5p-stimulated inflammatory cytokines production and NF-κB activation.

CONCLUSIONS: Curcumin attenuated neuroinflammation induced by LPS through regulating miR-199b-5p/IKKβ/NF-κB axis in microglia.

Keywords: Curcumin, Inflammation Mediators, Microglia, Anti-Inflammatory Agents, I-kappa B Kinase, I-kappa B Proteins, Lipopolysaccharides, Neuroimmunomodulation, Nitric Oxide Synthase Type II, Protein Serine-Threonine Kinases, Spinal Cord Injuries, Transcription Factor RelA