Curcumin Alleviates Lipopolysaccharide (LPS)-Activated Neuroinflammation via Modulation of miR-199b-5p/IκB Kinase β (IKKβ)/Nuclear Factor Kappa B (NF-κB) Pathway in Microglia
Feng Gao, Juan Shen, Lin Zhao, Qin Hao, Yanling Yang
Department of Physiology, School of Medicine of Yan’an University, Yan’an, Shaanxi, China (mainland)
Med Sci Monit 2019; 25:9801-9810
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)-alpha, interleukin (IL)-1ß, and IkappaB kinase ß (IKKß) 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 IKKß 3’UTR were predicted by bioinformatics, and direct interaction between miR-199b-5p and IKKß 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-kappaB) 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-alpha, and IL-1ß. Moreover, curcumin increased the level of miR-199b-5p and decreased IKKß expression in activated microglial cells. Knockdown of miR-199b-5p or overexpression of IKKß reversed the inhibitory effect of curcumin on inflammatory response and NF-kappaB activation. MiR-199b-5p directly targeted IKKß and suppressed its expression. Silencing of IKKß abolished miR-199b-5p-stimulated inflammatory cytokines production and NF-kappaB activation.
CONCLUSIONS: Curcumin attenuated neuroinflammation induced by LPS through regulating miR-199b-5p/IKKß/NF-kappaB axis in microglia.
Keywords: Curcumin, Inflammation Mediators, Microglia