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Artemisinin Attenuates Lipopolysaccharide-Stimulated Proinflammatory Responses by Inhibiting NF-κB Pathway in Microglia Cells
Microglial activation plays an important role in neuroinflammation, which contributes to neuronal damage, and inhibition of microglial activation may have therapeutic benefits that could alleviate the progression of neurodegeneration. Recent studies have indicated that the antimalarial agent artemis...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325975/ https://www.ncbi.nlm.nih.gov/pubmed/22514713 http://dx.doi.org/10.1371/journal.pone.0035125 |
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author | Zhu, Cansheng Xiong, Zhaojun Chen, Xiaohong Peng, Fuhua Hu, Xueqiang Chen, Yanming Wang, Qing |
author_facet | Zhu, Cansheng Xiong, Zhaojun Chen, Xiaohong Peng, Fuhua Hu, Xueqiang Chen, Yanming Wang, Qing |
author_sort | Zhu, Cansheng |
collection | PubMed |
description | Microglial activation plays an important role in neuroinflammation, which contributes to neuronal damage, and inhibition of microglial activation may have therapeutic benefits that could alleviate the progression of neurodegeneration. Recent studies have indicated that the antimalarial agent artemisinin has the ability to inhibit NF-κB activation. In this study, the inhibitory effects of artemisinin on the production of proinflammatory mediators were investigated in lipopolysaccharide (LPS)-stimulated primary microglia. Our results show that artemisinin significantly inhibited LPS-induced production of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1) and nitric oxide (NO). Artemisinin significantly decreased both the mRNA and the protein levels of these pro-inflammatory cytokines and inducible nitric oxide synthase (iNOS) and increased the protein levels of IκB-α, which forms a cytoplasmic inactive complex with the p65-p50 heterodimeric complex. Artemisinin treatment significantly inhibited basal and LPS-induced migration of BV-2 microglia. Electrophoretic mobility shift assays revealed increased NF-κB binding activity in LPS-stimulated primary microglia, and this increase could be prevented by artemisinin. The inhibitory effects of artemisinin on LPS-stimulated microglia were blocked after IκB-α was silenced with IκB-α siRNA. Our results suggest that artemisinin is able to inhibit neuroinflammation by interfering with NF-κB signaling. The data provide direct evidence of the potential application of artemisinin for the treatment of neuroinflammatory diseases. |
format | Online Article Text |
id | pubmed-3325975 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33259752012-04-18 Artemisinin Attenuates Lipopolysaccharide-Stimulated Proinflammatory Responses by Inhibiting NF-κB Pathway in Microglia Cells Zhu, Cansheng Xiong, Zhaojun Chen, Xiaohong Peng, Fuhua Hu, Xueqiang Chen, Yanming Wang, Qing PLoS One Research Article Microglial activation plays an important role in neuroinflammation, which contributes to neuronal damage, and inhibition of microglial activation may have therapeutic benefits that could alleviate the progression of neurodegeneration. Recent studies have indicated that the antimalarial agent artemisinin has the ability to inhibit NF-κB activation. In this study, the inhibitory effects of artemisinin on the production of proinflammatory mediators were investigated in lipopolysaccharide (LPS)-stimulated primary microglia. Our results show that artemisinin significantly inhibited LPS-induced production of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1) and nitric oxide (NO). Artemisinin significantly decreased both the mRNA and the protein levels of these pro-inflammatory cytokines and inducible nitric oxide synthase (iNOS) and increased the protein levels of IκB-α, which forms a cytoplasmic inactive complex with the p65-p50 heterodimeric complex. Artemisinin treatment significantly inhibited basal and LPS-induced migration of BV-2 microglia. Electrophoretic mobility shift assays revealed increased NF-κB binding activity in LPS-stimulated primary microglia, and this increase could be prevented by artemisinin. The inhibitory effects of artemisinin on LPS-stimulated microglia were blocked after IκB-α was silenced with IκB-α siRNA. Our results suggest that artemisinin is able to inhibit neuroinflammation by interfering with NF-κB signaling. The data provide direct evidence of the potential application of artemisinin for the treatment of neuroinflammatory diseases. Public Library of Science 2012-04-13 /pmc/articles/PMC3325975/ /pubmed/22514713 http://dx.doi.org/10.1371/journal.pone.0035125 Text en Zhu et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Zhu, Cansheng Xiong, Zhaojun Chen, Xiaohong Peng, Fuhua Hu, Xueqiang Chen, Yanming Wang, Qing Artemisinin Attenuates Lipopolysaccharide-Stimulated Proinflammatory Responses by Inhibiting NF-κB Pathway in Microglia Cells |
title | Artemisinin Attenuates Lipopolysaccharide-Stimulated Proinflammatory Responses by Inhibiting NF-κB Pathway in Microglia Cells |
title_full | Artemisinin Attenuates Lipopolysaccharide-Stimulated Proinflammatory Responses by Inhibiting NF-κB Pathway in Microglia Cells |
title_fullStr | Artemisinin Attenuates Lipopolysaccharide-Stimulated Proinflammatory Responses by Inhibiting NF-κB Pathway in Microglia Cells |
title_full_unstemmed | Artemisinin Attenuates Lipopolysaccharide-Stimulated Proinflammatory Responses by Inhibiting NF-κB Pathway in Microglia Cells |
title_short | Artemisinin Attenuates Lipopolysaccharide-Stimulated Proinflammatory Responses by Inhibiting NF-κB Pathway in Microglia Cells |
title_sort | artemisinin attenuates lipopolysaccharide-stimulated proinflammatory responses by inhibiting nf-κb pathway in microglia cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325975/ https://www.ncbi.nlm.nih.gov/pubmed/22514713 http://dx.doi.org/10.1371/journal.pone.0035125 |
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