Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Hui-Na, Xiang, Qiu-An, Lin, Hao-Hui, Chen, Jie-Ning, Guo, Wen-Jie, Guo, Wan-Meng, Yue, Xiang-Ning, Zhao, Zhen-Fu, Ji, Kunmei, Chen, Jia-Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912031/
https://www.ncbi.nlm.nih.gov/pubmed/35268679
http://dx.doi.org/10.3390/molecules27051577
_version_ 1784667000039014400
author Wang, Hui-Na
Xiang, Qiu-An
Lin, Hao-Hui
Chen, Jie-Ning
Guo, Wen-Jie
Guo, Wan-Meng
Yue, Xiang-Ning
Zhao, Zhen-Fu
Ji, Kunmei
Chen, Jia-Jie
author_facet Wang, Hui-Na
Xiang, Qiu-An
Lin, Hao-Hui
Chen, Jie-Ning
Guo, Wen-Jie
Guo, Wan-Meng
Yue, Xiang-Ning
Zhao, Zhen-Fu
Ji, Kunmei
Chen, Jia-Jie
author_sort Wang, Hui-Na
collection PubMed
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.
format Online
Article
Text
id pubmed-8912031
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-89120312022-03-11 Plant-Derived Molecule 4-Methylumbelliferone Suppresses FcεRI-Mediated Mast Cell Activation and Allergic Inflammation Wang, Hui-Na Xiang, Qiu-An Lin, Hao-Hui Chen, Jie-Ning Guo, Wen-Jie Guo, Wan-Meng Yue, Xiang-Ning Zhao, Zhen-Fu Ji, Kunmei Chen, Jia-Jie Molecules Article 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. MDPI 2022-02-27 /pmc/articles/PMC8912031/ /pubmed/35268679 http://dx.doi.org/10.3390/molecules27051577 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Hui-Na
Xiang, Qiu-An
Lin, Hao-Hui
Chen, Jie-Ning
Guo, Wen-Jie
Guo, Wan-Meng
Yue, Xiang-Ning
Zhao, Zhen-Fu
Ji, Kunmei
Chen, Jia-Jie
Plant-Derived Molecule 4-Methylumbelliferone Suppresses FcεRI-Mediated Mast Cell Activation and Allergic Inflammation
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912031/
https://www.ncbi.nlm.nih.gov/pubmed/35268679
http://dx.doi.org/10.3390/molecules27051577
work_keys_str_mv AT wanghuina plantderivedmolecule4methylumbelliferonesuppressesfcerimediatedmastcellactivationandallergicinflammation
AT xiangqiuan plantderivedmolecule4methylumbelliferonesuppressesfcerimediatedmastcellactivationandallergicinflammation
AT linhaohui plantderivedmolecule4methylumbelliferonesuppressesfcerimediatedmastcellactivationandallergicinflammation
AT chenjiening plantderivedmolecule4methylumbelliferonesuppressesfcerimediatedmastcellactivationandallergicinflammation
AT guowenjie plantderivedmolecule4methylumbelliferonesuppressesfcerimediatedmastcellactivationandallergicinflammation
AT guowanmeng plantderivedmolecule4methylumbelliferonesuppressesfcerimediatedmastcellactivationandallergicinflammation
AT yuexiangning plantderivedmolecule4methylumbelliferonesuppressesfcerimediatedmastcellactivationandallergicinflammation
AT zhaozhenfu plantderivedmolecule4methylumbelliferonesuppressesfcerimediatedmastcellactivationandallergicinflammation
AT jikunmei plantderivedmolecule4methylumbelliferonesuppressesfcerimediatedmastcellactivationandallergicinflammation
AT chenjiajie plantderivedmolecule4methylumbelliferonesuppressesfcerimediatedmastcellactivationandallergicinflammation