Plant-Derived Molecule 4-Methylumbelliferone Suppresses FcεRI-Mediated Mast Cell Activation and Allergic Inflammation
Mast cells (MCs) are an important treatment target for high-affinity IgE Fc receptor (FcεRI)-mediated allergic diseases. The plant-derived molecule 4-methylumbelliferone (4-MU) has beneficial effects in animal models of inflammation and autoimmunity diseases. The aim of this study was to examine 4-M...
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MDPI AG
2022-02-01
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| Online Access: | https://www.mdpi.com/1420-3049/27/5/1577 |
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| author | Hui-Na Wang Qiu-An Xiang Hao-Hui Lin Jie-Ning Chen Wen-Jie Guo Wan-Meng Guo Xiang-Ning Yue Zhen-Fu Zhao Kunmei Ji Jia-Jie Chen |
| author_facet | Hui-Na Wang Qiu-An Xiang Hao-Hui Lin Jie-Ning Chen Wen-Jie Guo Wan-Meng Guo Xiang-Ning Yue Zhen-Fu Zhao Kunmei Ji Jia-Jie Chen |
| author_sort | Hui-Na Wang |
| collection | DOAJ |
| description | Mast cells (MCs) are an important treatment target for high-affinity IgE Fc receptor (FcεRI)-mediated allergic diseases. The plant-derived molecule 4-methylumbelliferone (4-MU) has beneficial effects in animal models of inflammation and autoimmunity diseases. The aim of this study was to examine 4-MU effects on MC activation and probe the underlying molecular mechanism(s). We sensitized rat basophilic leukemia cells (RBLs) and mouse bone marrow-derived mast cells (BMMCs) with anti-dinitrophenol (DNP) immunoglobulin (Ig)E antibodies, stimulated them with exposure to DNP-human serum albumin (HSA), and then treated stimulated cells with 4-MU. Signaling-protein expression was determined by immunoblotting. In vivo allergic responses were examined in IgE-mediated passive cutaneous anaphylaxis (PCA) and ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) mouse models. 4-MU inhibited β-hexosaminidase activity and histamine release dose-dependently in FcεRI-activated RBLs and BMMCs. Additionally, 4-MU reduced cytomorphological elongation and F-actin reorganization while down-regulating IgE/Ag-induced phosphorylation of SYK, NF-κB p65, ERK1/2, p38, and JNK. Moreover, 4-MU attenuated the PCA allergic reaction (i.e., less ear thickening and dye extravasation). Similarly, we found that 4-MU decreased body temperature, serum histamine, and IL4 secretion in OVA-challenged ASA model mice. In conclusion, 4-MU had a suppressing effect on MC activation both in vitro and in vivo and thus may represent a new strategy for treating IgE-mediated allergic conditions. |
| first_indexed | 2024-03-09T20:30:01Z |
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| language | English |
| last_indexed | 2024-03-09T20:30:01Z |
| publishDate | 2022-02-01 |
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| series | Molecules |
| spelling | doaj.art-4f5a5044967b47e1a00c39c0ba40e4812023-11-23T23:26:34ZengMDPI AGMolecules1420-30492022-02-01275157710.3390/molecules27051577Plant-Derived Molecule 4-Methylumbelliferone Suppresses FcεRI-Mediated Mast Cell Activation and Allergic InflammationHui-Na Wang0Qiu-An Xiang1Hao-Hui Lin2Jie-Ning Chen3Wen-Jie Guo4Wan-Meng Guo5Xiang-Ning Yue6Zhen-Fu Zhao7Kunmei Ji8Jia-Jie Chen9Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, ChinaMast cells (MCs) are an important treatment target for high-affinity IgE Fc receptor (FcεRI)-mediated allergic diseases. The plant-derived molecule 4-methylumbelliferone (4-MU) has beneficial effects in animal models of inflammation and autoimmunity diseases. The aim of this study was to examine 4-MU effects on MC activation and probe the underlying molecular mechanism(s). We sensitized rat basophilic leukemia cells (RBLs) and mouse bone marrow-derived mast cells (BMMCs) with anti-dinitrophenol (DNP) immunoglobulin (Ig)E antibodies, stimulated them with exposure to DNP-human serum albumin (HSA), and then treated stimulated cells with 4-MU. Signaling-protein expression was determined by immunoblotting. In vivo allergic responses were examined in IgE-mediated passive cutaneous anaphylaxis (PCA) and ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) mouse models. 4-MU inhibited β-hexosaminidase activity and histamine release dose-dependently in FcεRI-activated RBLs and BMMCs. Additionally, 4-MU reduced cytomorphological elongation and F-actin reorganization while down-regulating IgE/Ag-induced phosphorylation of SYK, NF-κB p65, ERK1/2, p38, and JNK. Moreover, 4-MU attenuated the PCA allergic reaction (i.e., less ear thickening and dye extravasation). Similarly, we found that 4-MU decreased body temperature, serum histamine, and IL4 secretion in OVA-challenged ASA model mice. In conclusion, 4-MU had a suppressing effect on MC activation both in vitro and in vivo and thus may represent a new strategy for treating IgE-mediated allergic conditions.https://www.mdpi.com/1420-3049/27/5/15774-methylumbelliferonemast cellFcεRI signalingSYK |
| spellingShingle | Hui-Na Wang Qiu-An Xiang Hao-Hui Lin Jie-Ning Chen Wen-Jie Guo Wan-Meng Guo Xiang-Ning Yue Zhen-Fu Zhao Kunmei Ji Jia-Jie Chen Plant-Derived Molecule 4-Methylumbelliferone Suppresses FcεRI-Mediated Mast Cell Activation and Allergic Inflammation Molecules 4-methylumbelliferone mast cell FcεRI signaling SYK |
| title | Plant-Derived Molecule 4-Methylumbelliferone Suppresses FcεRI-Mediated Mast Cell Activation and Allergic Inflammation |
| title_full | Plant-Derived Molecule 4-Methylumbelliferone Suppresses FcεRI-Mediated Mast Cell Activation and Allergic Inflammation |
| title_fullStr | Plant-Derived Molecule 4-Methylumbelliferone Suppresses FcεRI-Mediated Mast Cell Activation and Allergic Inflammation |
| title_full_unstemmed | Plant-Derived Molecule 4-Methylumbelliferone Suppresses FcεRI-Mediated Mast Cell Activation and Allergic Inflammation |
| title_short | Plant-Derived Molecule 4-Methylumbelliferone Suppresses FcεRI-Mediated Mast Cell Activation and Allergic Inflammation |
| title_sort | plant derived molecule 4 methylumbelliferone suppresses fcεri mediated mast cell activation and allergic inflammation |
| topic | 4-methylumbelliferone mast cell FcεRI signaling SYK |
| url | https://www.mdpi.com/1420-3049/27/5/1577 |
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