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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Scientific Literature, Inc.
2019
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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. |
format | Online Article Text |
id | pubmed-6937907 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | International Scientific Literature, Inc. |
record_format | MEDLINE/PubMed |
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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