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Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expression
BACKGROUND: It is well known that most neurodegenerative diseases are associated with microglia-mediated inflammation. Our previous research demonstrates that the CD40 signaling is critically involved in microglia-related immune responses in the brain. For example, it is well known that the activati...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2569027/ https://www.ncbi.nlm.nih.gov/pubmed/18817573 http://dx.doi.org/10.1186/1742-2094-5-41 |
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author | Rezai-Zadeh, Kavon Ehrhart, Jared Bai, Yun Sanberg, Paul R Bickford, Paula Tan, Jun Shytle, R Douglas |
author_facet | Rezai-Zadeh, Kavon Ehrhart, Jared Bai, Yun Sanberg, Paul R Bickford, Paula Tan, Jun Shytle, R Douglas |
author_sort | Rezai-Zadeh, Kavon |
collection | PubMed |
description | BACKGROUND: It is well known that most neurodegenerative diseases are associated with microglia-mediated inflammation. Our previous research demonstrates that the CD40 signaling is critically involved in microglia-related immune responses in the brain. For example, it is well known that the activation of the signal transducer and activator of transcription (STAT) signaling pathway plays a central role in interferon-gamma (IFN-γ)-induced microglial CD40 expression. We and others have previously reported that microglial CD40 expression is significantly induced by IFN-γ and amyloid-β (Aβ) peptide. Recent studies have shown that certain flavonoids possess anti-inflammatory and neuroprotective properties distinct from their well-known anti-oxidant effects. In particular, flavonoids, apigenin and luteolin have been found to be effective CD40 immunomodulators. METHODS: Cultured microglia, both N9 and primary derived lines, were treated with flavonoids in the presence of IFN-γ and/or CD40 ligation to assess any anti-inflammatory effects and/or mechanisms. CD40 expression on microglia was analyzed by fluorescence activated cell sorting (FACS). Anti-inflammatory effects and mechanisms were confirmed by ELISA for interlekin-6 (IL-6) and TNF-α, lactate dehydrogenase (LDH) assay, and STAT1 Western blotting. RESULTS: Apigenin and luteolin concentration-dependently suppressed IFN-γ-induced CD40 expression. Apigenin and luteolin also suppressed microglial TNF-α and IL-6 production stimulated by IFN-gamma challenge in the presence of CD40 ligation. In addition, apigenin and luteolin markedly inhibited IFN-γ-induced phosphorylation of STAT1 with little impact on cell survival. CONCLUSION: Our findings provide further support for apigenin and luteolin's anti-inflammatory effects and suggest that these flavonoids may have neuroprotective/disease-modifying properties in various neurodegenerative disorders, including Alzheimer's disease (AD). |
format | Text |
id | pubmed-2569027 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-25690272008-10-17 Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expression Rezai-Zadeh, Kavon Ehrhart, Jared Bai, Yun Sanberg, Paul R Bickford, Paula Tan, Jun Shytle, R Douglas J Neuroinflammation Research BACKGROUND: It is well known that most neurodegenerative diseases are associated with microglia-mediated inflammation. Our previous research demonstrates that the CD40 signaling is critically involved in microglia-related immune responses in the brain. For example, it is well known that the activation of the signal transducer and activator of transcription (STAT) signaling pathway plays a central role in interferon-gamma (IFN-γ)-induced microglial CD40 expression. We and others have previously reported that microglial CD40 expression is significantly induced by IFN-γ and amyloid-β (Aβ) peptide. Recent studies have shown that certain flavonoids possess anti-inflammatory and neuroprotective properties distinct from their well-known anti-oxidant effects. In particular, flavonoids, apigenin and luteolin have been found to be effective CD40 immunomodulators. METHODS: Cultured microglia, both N9 and primary derived lines, were treated with flavonoids in the presence of IFN-γ and/or CD40 ligation to assess any anti-inflammatory effects and/or mechanisms. CD40 expression on microglia was analyzed by fluorescence activated cell sorting (FACS). Anti-inflammatory effects and mechanisms were confirmed by ELISA for interlekin-6 (IL-6) and TNF-α, lactate dehydrogenase (LDH) assay, and STAT1 Western blotting. RESULTS: Apigenin and luteolin concentration-dependently suppressed IFN-γ-induced CD40 expression. Apigenin and luteolin also suppressed microglial TNF-α and IL-6 production stimulated by IFN-gamma challenge in the presence of CD40 ligation. In addition, apigenin and luteolin markedly inhibited IFN-γ-induced phosphorylation of STAT1 with little impact on cell survival. CONCLUSION: Our findings provide further support for apigenin and luteolin's anti-inflammatory effects and suggest that these flavonoids may have neuroprotective/disease-modifying properties in various neurodegenerative disorders, including Alzheimer's disease (AD). BioMed Central 2008-09-25 /pmc/articles/PMC2569027/ /pubmed/18817573 http://dx.doi.org/10.1186/1742-2094-5-41 Text en Copyright © 2008 Rezai-Zadeh et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Rezai-Zadeh, Kavon Ehrhart, Jared Bai, Yun Sanberg, Paul R Bickford, Paula Tan, Jun Shytle, R Douglas Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expression |
title | Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expression |
title_full | Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expression |
title_fullStr | Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expression |
title_full_unstemmed | Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expression |
title_short | Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expression |
title_sort | apigenin and luteolin modulate microglial activation via inhibition of stat1-induced cd40 expression |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2569027/ https://www.ncbi.nlm.nih.gov/pubmed/18817573 http://dx.doi.org/10.1186/1742-2094-5-41 |
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