Chrysin Inhibits NF-κB-Dependent <i>CCL5</i> Transcription by Targeting IκB Kinase in the Atopic Dermatitis-Like Inflammatory Microenvironment
Chrysin (5,7-dihydroxyflavone) is a natural polyphenolic compound that induces an anti-inflammatory response. In this study, we investigated the molecular mechanism underlying the chrysin-induced suppression of C-C motif chemokine ligand 5 (<i>CCL5</i>) gene expression in atopic dermatit...
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MDPI AG
2020-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/19/7348 |
| _version_ | 1797551762831310848 |
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| author | Hyunjin Yeo Young Han Lee Dongsoo Koh Yoongho Lim Soon Young Shin |
| author_facet | Hyunjin Yeo Young Han Lee Dongsoo Koh Yoongho Lim Soon Young Shin |
| author_sort | Hyunjin Yeo |
| collection | DOAJ |
| description | Chrysin (5,7-dihydroxyflavone) is a natural polyphenolic compound that induces an anti-inflammatory response. In this study, we investigated the molecular mechanism underlying the chrysin-induced suppression of C-C motif chemokine ligand 5 (<i>CCL5</i>) gene expression in atopic dermatitis (AD)-like inflammatory microenvironment. We showed that chrysin inhibited <i>CCL5</i> expression at the transcriptional level through the suppression of nuclear factor kappa B (NF-κB) in the inflammatory environment. Chrysin could bind to the ATP-binding pocket of the inhibitor of κB (IκB) kinase (IKK) and, subsequently, prevent IκB degradation and NF-κB activation. The clinical efficacy of chrysin in targeting IKK was evaluated in 2,4-dinitrochlorobenzene-induced skin lesions in BALB/c mice. Our results suggested that chrysin prevented <i>CCL5</i> expression by targeting IKK to reduce the infiltration of mast cells to the inflammatory sites and at least partially attenuate the inflammatory responses. These findings suggested that chrysin might be useful as a platform for the design and synthesis of small-molecule IKK-targeting drugs for the treatment of chronic inflammatory diseases, such as AD. |
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| format | Article |
| id | doaj.art-4a7b9533bfe14e6b8744e057edd4452c |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:50:35Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4a7b9533bfe14e6b8744e057edd4452c2023-11-20T16:05:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012119734810.3390/ijms21197348Chrysin Inhibits NF-κB-Dependent <i>CCL5</i> Transcription by Targeting IκB Kinase in the Atopic Dermatitis-Like Inflammatory MicroenvironmentHyunjin Yeo0Young Han Lee1Dongsoo Koh2Yoongho Lim3Soon Young Shin4Department of Biological Sciences, Sanghuh College of Lifesciences, Konkuk University, Seoul 05029, KoreaDepartment of Biological Sciences, Sanghuh College of Lifesciences, Konkuk University, Seoul 05029, KoreaDepartment of Applied Chemistry, Dongduk Women’s University, Seoul 02748, KoreaDivision of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul 05029, KoreaDepartment of Biological Sciences, Sanghuh College of Lifesciences, Konkuk University, Seoul 05029, KoreaChrysin (5,7-dihydroxyflavone) is a natural polyphenolic compound that induces an anti-inflammatory response. In this study, we investigated the molecular mechanism underlying the chrysin-induced suppression of C-C motif chemokine ligand 5 (<i>CCL5</i>) gene expression in atopic dermatitis (AD)-like inflammatory microenvironment. We showed that chrysin inhibited <i>CCL5</i> expression at the transcriptional level through the suppression of nuclear factor kappa B (NF-κB) in the inflammatory environment. Chrysin could bind to the ATP-binding pocket of the inhibitor of κB (IκB) kinase (IKK) and, subsequently, prevent IκB degradation and NF-κB activation. The clinical efficacy of chrysin in targeting IKK was evaluated in 2,4-dinitrochlorobenzene-induced skin lesions in BALB/c mice. Our results suggested that chrysin prevented <i>CCL5</i> expression by targeting IKK to reduce the infiltration of mast cells to the inflammatory sites and at least partially attenuate the inflammatory responses. These findings suggested that chrysin might be useful as a platform for the design and synthesis of small-molecule IKK-targeting drugs for the treatment of chronic inflammatory diseases, such as AD.https://www.mdpi.com/1422-0067/21/19/7348atopic dermatitisCCL5chemokinechrysinmast cell |
| spellingShingle | Hyunjin Yeo Young Han Lee Dongsoo Koh Yoongho Lim Soon Young Shin Chrysin Inhibits NF-κB-Dependent <i>CCL5</i> Transcription by Targeting IκB Kinase in the Atopic Dermatitis-Like Inflammatory Microenvironment International Journal of Molecular Sciences atopic dermatitis CCL5 chemokine chrysin mast cell |
| title | Chrysin Inhibits NF-κB-Dependent <i>CCL5</i> Transcription by Targeting IκB Kinase in the Atopic Dermatitis-Like Inflammatory Microenvironment |
| title_full | Chrysin Inhibits NF-κB-Dependent <i>CCL5</i> Transcription by Targeting IκB Kinase in the Atopic Dermatitis-Like Inflammatory Microenvironment |
| title_fullStr | Chrysin Inhibits NF-κB-Dependent <i>CCL5</i> Transcription by Targeting IκB Kinase in the Atopic Dermatitis-Like Inflammatory Microenvironment |
| title_full_unstemmed | Chrysin Inhibits NF-κB-Dependent <i>CCL5</i> Transcription by Targeting IκB Kinase in the Atopic Dermatitis-Like Inflammatory Microenvironment |
| title_short | Chrysin Inhibits NF-κB-Dependent <i>CCL5</i> Transcription by Targeting IκB Kinase in the Atopic Dermatitis-Like Inflammatory Microenvironment |
| title_sort | chrysin inhibits nf κb dependent i ccl5 i transcription by targeting iκb kinase in the atopic dermatitis like inflammatory microenvironment |
| topic | atopic dermatitis CCL5 chemokine chrysin mast cell |
| url | https://www.mdpi.com/1422-0067/21/19/7348 |
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