Chrysin Inhibits TNFα-Induced TSLP Expression through Downregulation of EGR1 Expression in Keratinocytes
Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that acts as a critical mediator in the pathogenesis of atopic dermatitis (AD). Various therapeutic agents that prevent TSLP function can efficiently relieve the clinical symptoms of AD. However, the downregulation of TSLP ex...
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MDPI AG
2021-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/9/4350 |
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| author | Hyunjin Yeo Young Han Lee Sung Shin Ahn Euitaek Jung Yoongho Lim Soon Young Shin |
| author_facet | Hyunjin Yeo Young Han Lee Sung Shin Ahn Euitaek Jung Yoongho Lim Soon Young Shin |
| author_sort | Hyunjin Yeo |
| collection | DOAJ |
| description | Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that acts as a critical mediator in the pathogenesis of atopic dermatitis (AD). Various therapeutic agents that prevent TSLP function can efficiently relieve the clinical symptoms of AD. However, the downregulation of TSLP expression by therapeutic agents remains poorly understood. In this study, we investigated the mode of action of chrysin in TSLP suppression in an AD-like inflammatory environment. We observed that the transcription factor early growth response (EGR1) contributed to the tumor necrosis factor alpha (TNFα)-induced transcription of <i>TSLP</i>. Chrysin attenuated TNFα-induced TSLP expression by downregulating EGR1 expression in HaCaT keratinocytes. We also showed that the oral administration of chrysin improved AD-like skin lesions in the ear and neck of BALB/c mice challenged with 2,4-dinitrochlorobenzene. We also showed that chrysin suppressed the expression of EGR1 and TSLP by inhibiting the extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) 1/2 mitogen-activated protein kinase pathways. Collectively, the findings of this study suggest that chrysin improves AD-like skin lesions, at least in part, through the downregulation of the ERK1/2 or JNK1/2-EGR1-TSLP signaling axis in keratinocytes. |
| first_indexed | 2024-03-10T12:06:13Z |
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| id | doaj.art-ea22a19ff37045f8a44054694a4e9c2b |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:06:13Z |
| publishDate | 2021-04-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ea22a19ff37045f8a44054694a4e9c2b2023-11-21T16:34:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01229435010.3390/ijms22094350Chrysin Inhibits TNFα-Induced TSLP Expression through Downregulation of EGR1 Expression in KeratinocytesHyunjin Yeo0Young Han Lee1Sung Shin Ahn2Euitaek Jung3Yoongho Lim4Soon Young Shin5Department 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 Biological Sciences, Sanghuh College of Lifesciences, Konkuk University, Seoul 05029, KoreaDepartment of Biological Sciences, Sanghuh College of Lifesciences, Konkuk University, Seoul 05029, KoreaDivision of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul 05029, KoreaDepartment of Biological Sciences, Sanghuh College of Lifesciences, Konkuk University, Seoul 05029, KoreaThymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that acts as a critical mediator in the pathogenesis of atopic dermatitis (AD). Various therapeutic agents that prevent TSLP function can efficiently relieve the clinical symptoms of AD. However, the downregulation of TSLP expression by therapeutic agents remains poorly understood. In this study, we investigated the mode of action of chrysin in TSLP suppression in an AD-like inflammatory environment. We observed that the transcription factor early growth response (EGR1) contributed to the tumor necrosis factor alpha (TNFα)-induced transcription of <i>TSLP</i>. Chrysin attenuated TNFα-induced TSLP expression by downregulating EGR1 expression in HaCaT keratinocytes. We also showed that the oral administration of chrysin improved AD-like skin lesions in the ear and neck of BALB/c mice challenged with 2,4-dinitrochlorobenzene. We also showed that chrysin suppressed the expression of EGR1 and TSLP by inhibiting the extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) 1/2 mitogen-activated protein kinase pathways. Collectively, the findings of this study suggest that chrysin improves AD-like skin lesions, at least in part, through the downregulation of the ERK1/2 or JNK1/2-EGR1-TSLP signaling axis in keratinocytes.https://www.mdpi.com/1422-0067/22/9/4350atopic dermatitischrysin2,4-dinitrochlorobenzeneearly growth response 1thymic stromal lymphopoietin |
| spellingShingle | Hyunjin Yeo Young Han Lee Sung Shin Ahn Euitaek Jung Yoongho Lim Soon Young Shin Chrysin Inhibits TNFα-Induced TSLP Expression through Downregulation of EGR1 Expression in Keratinocytes International Journal of Molecular Sciences atopic dermatitis chrysin 2,4-dinitrochlorobenzene early growth response 1 thymic stromal lymphopoietin |
| title | Chrysin Inhibits TNFα-Induced TSLP Expression through Downregulation of EGR1 Expression in Keratinocytes |
| title_full | Chrysin Inhibits TNFα-Induced TSLP Expression through Downregulation of EGR1 Expression in Keratinocytes |
| title_fullStr | Chrysin Inhibits TNFα-Induced TSLP Expression through Downregulation of EGR1 Expression in Keratinocytes |
| title_full_unstemmed | Chrysin Inhibits TNFα-Induced TSLP Expression through Downregulation of EGR1 Expression in Keratinocytes |
| title_short | Chrysin Inhibits TNFα-Induced TSLP Expression through Downregulation of EGR1 Expression in Keratinocytes |
| title_sort | chrysin inhibits tnfα induced tslp expression through downregulation of egr1 expression in keratinocytes |
| topic | atopic dermatitis chrysin 2,4-dinitrochlorobenzene early growth response 1 thymic stromal lymphopoietin |
| url | https://www.mdpi.com/1422-0067/22/9/4350 |
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