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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

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 in...

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Autores principales: Gao, Feng, Shen, Juan, Zhao, Lin, Hao, Qin, Yang, Yanling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937907/
https://www.ncbi.nlm.nih.gov/pubmed/31862869
http://dx.doi.org/10.12659/MSM.918237
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author Gao, Feng
Shen, Juan
Zhao, Lin
Hao, Qin
Yang, Yanling
author_facet Gao, Feng
Shen, Juan
Zhao, Lin
Hao, Qin
Yang, Yanling
author_sort Gao, Feng
collection PubMed
description 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/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.
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spelling pubmed-69379072020-01-06 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 Gao, Feng Shen, Juan Zhao, Lin Hao, Qin Yang, Yanling Med Sci Monit Lab/In Vitro Research 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/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. International Scientific Literature, Inc. 2019-12-21 /pmc/articles/PMC6937907/ /pubmed/31862869 http://dx.doi.org/10.12659/MSM.918237 Text en © Med Sci Monit, 2019 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) )
spellingShingle Lab/In Vitro Research
Gao, Feng
Shen, Juan
Zhao, Lin
Hao, Qin
Yang, Yanling
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Lab/In Vitro Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937907/
https://www.ncbi.nlm.nih.gov/pubmed/31862869
http://dx.doi.org/10.12659/MSM.918237
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