Resveratrol inhibits MRGPRX2-mediated mast cell activation via Nrf2 pathway
Copyright © 2021. Published by Elsevier B.V..
Mast cells (MCs) are crucial effectors in inflammation and allergic reactions. The Mas-related G-protein-coupled receptor X2 (MRGPRX2) was the MC-specific receptor and play a key role in IgE-independent allergic reactions. The activation of the Nuclear factor erythroid derived 2-related factor 2 (Nrf2) is involved in IgE-mediated MC degranulation. Resveratrol (Res) is a polyphenolic compound in red wine and has been reported to exert a variety of pharmacological effects. In the current study, we investigated the effect of Res in regulating MRGPRX2-mediated MC activation and its underlyingmechanism. We demonstrated that Res reduced compound 48/80 (C48/80)-induced calcium flux in MCs and inhibited MCs degranulation in vitro. Res also suppressed C48/80-induced hind paw extravasation, active systemic anaphylaxis, and MCs degranulation in mouse models of pseudo-allergy in vivo. Furthermore, PCR and immunohistochemistry assay suggest that Res up-regulates Nrf2 expression and Nrf2 inhibitor attenuates the protective effects of Res. In conclusion, Res exerts an inhibitory effect on MRGPRX2-mediated MCs activation by targeting Nrf2 pathway and may present a promising new therapeutic agent for the treatment of MRGPRX2-dependent anaphylactoid reactions.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:93 |
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| Enthalten in: |
International immunopharmacology - 93(2021) vom: 01. Apr., Seite 107426 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Jue [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-Allergic Agents |
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| Anmerkungen: |
Date Completed 28.05.2021 Date Revised 28.05.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.intimp.2021.107426 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM321105648 |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021. Published by Elsevier B.V. | ||
| 520 | |a Mast cells (MCs) are crucial effectors in inflammation and allergic reactions. The Mas-related G-protein-coupled receptor X2 (MRGPRX2) was the MC-specific receptor and play a key role in IgE-independent allergic reactions. The activation of the Nuclear factor erythroid derived 2-related factor 2 (Nrf2) is involved in IgE-mediated MC degranulation. Resveratrol (Res) is a polyphenolic compound in red wine and has been reported to exert a variety of pharmacological effects. In the current study, we investigated the effect of Res in regulating MRGPRX2-mediated MC activation and its underlyingmechanism. We demonstrated that Res reduced compound 48/80 (C48/80)-induced calcium flux in MCs and inhibited MCs degranulation in vitro. Res also suppressed C48/80-induced hind paw extravasation, active systemic anaphylaxis, and MCs degranulation in mouse models of pseudo-allergy in vivo. Furthermore, PCR and immunohistochemistry assay suggest that Res up-regulates Nrf2 expression and Nrf2 inhibitor attenuates the protective effects of Res. In conclusion, Res exerts an inhibitory effect on MRGPRX2-mediated MCs activation by targeting Nrf2 pathway and may present a promising new therapeutic agent for the treatment of MRGPRX2-dependent anaphylactoid reactions | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a MRGPRX2 | |
| 650 | 4 | |a Mast cell | |
| 650 | 4 | |a Nrf2 | |
| 650 | 4 | |a Resveratrol | |
| 650 | 7 | |a Anti-Allergic Agents |2 NLM | |
| 650 | 7 | |a Mrgprx2 protein, mouse |2 NLM | |
| 650 | 7 | |a NF-E2-Related Factor 2 |2 NLM | |
| 650 | 7 | |a Nfe2l2 protein, mouse |2 NLM | |
| 650 | 7 | |a Receptors, G-Protein-Coupled |2 NLM | |
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| 700 | 1 | |a Hu, Shiling |e verfasserin |4 aut | |
| 700 | 1 | |a Ge, Shuai |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Nan |e verfasserin |4 aut | |
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