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Title: Polydatin (PD) inhibits IgE-mediated passive cutaneous anaphylaxis in mice by stabilizing mast cells through modulating Ca{sup 2+} mobilization

Abstract

Mast cells play a key role in the pathogenesis of asthma and are a promising target for therapeutic intervention in asthma. This study investigated the effects of polydatin (PD), a resveratrol glucoside, on mast cell degranulation upon cross-linking of the high-affinity IgE receptors (FcεRI), as well as the anti-allergic activity of PD in vivo. Herein, we demonstrated that PD treatment for 30 min suppressed FcεRI-mediated mast cell degranulation in a dose-dependent manner. Concomitantly, PD significantly decreased FcεRI-mediated Ca{sup 2+} increase in mast cells. The suppressive effects of PD on FcεRI-mediated Ca{sup 2+} increase were largely inhibited by using LaCl{sub 3} to block the Ca{sup 2+} release-activated Ca{sup 2+} channels (CRACs). Furthermore, PD significantly inhibited Ca{sup 2+} entry through CRACs evoked by thapsigargin (TG). Knocking down protein expression of Orai1, the pore-forming subunit of CRACs, significantly decreased PD suppression of FcεRI-induced intracellular Ca{sup 2+} influx and mast cell degranulation. In a mouse model of mast cell-dependent passive cutaneous anaphylaxis (PCA), in vivo PD administration suppressed mast cell degranulation and inhibited anaphylaxis. Taken together, our data indicate that PD stabilizes mast cells by suppressing FcεRI-induced Ca{sup 2+} mobilization mainly through inhibiting Ca{sup 2+} entry via CRACs, thus exerting a protective effect againstmore » PCA. -- Highlights: ► Polydatin can prevent the pathogenesis of passive cutaneous anaphylaxis in mice. ► Polydatin stabilizes mast cells by decreasing FcεRI-mediated degranulation. ► Polydatin suppresses Ca{sup 2+} entry through CRAC channels in mast cells.« less

Authors:
 [1];  [2];  [3];  [4]; ;  [3];  [1];  [3];  [1]
  1. Department of Pathophysiology, School of Medicine, Shenzhen University, Shenzhen 518060 (China)
  2. (China)
  3. State Key Laboratory of Respiratory Disease for Allergy at Shengzhen University, Shenzhen 518060 (China)
  4. Shenzhen Entry-Exit Inspection and Quarantine Bureau, Shenzhen 518045 (China)
Publication Date:
OSTI Identifier:
22215967
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 264; Journal Issue: 3; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANAPHYLAXIS; ASTHMA; BROMIDES; CALCIUM; CROSS-LINKING; ENDOPLASMIC RETICULUM; IN VIVO; LANTHANUM CHLORIDES; MAST CELLS; MICE; OXYGEN; PATHOGENESIS; RECEPTORS

Citation Formats

Yuan, Meichun, Department of Physiology, Hubei University of Medicine, Shiyan, Li, Jianjie, Lv, Jingzhang, Mo, Xucheng, Yang, Chengbin, Chen, Xiangdong, Liu, Zhigang, and Liu, Jie, E-mail: ljljz@yahoo.com. Polydatin (PD) inhibits IgE-mediated passive cutaneous anaphylaxis in mice by stabilizing mast cells through modulating Ca{sup 2+} mobilization. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2012.08.024.
Yuan, Meichun, Department of Physiology, Hubei University of Medicine, Shiyan, Li, Jianjie, Lv, Jingzhang, Mo, Xucheng, Yang, Chengbin, Chen, Xiangdong, Liu, Zhigang, & Liu, Jie, E-mail: ljljz@yahoo.com. Polydatin (PD) inhibits IgE-mediated passive cutaneous anaphylaxis in mice by stabilizing mast cells through modulating Ca{sup 2+} mobilization. United States. doi:10.1016/J.TAAP.2012.08.024.
Yuan, Meichun, Department of Physiology, Hubei University of Medicine, Shiyan, Li, Jianjie, Lv, Jingzhang, Mo, Xucheng, Yang, Chengbin, Chen, Xiangdong, Liu, Zhigang, and Liu, Jie, E-mail: ljljz@yahoo.com. Thu . "Polydatin (PD) inhibits IgE-mediated passive cutaneous anaphylaxis in mice by stabilizing mast cells through modulating Ca{sup 2+} mobilization". United States. doi:10.1016/J.TAAP.2012.08.024.
@article{osti_22215967,
title = {Polydatin (PD) inhibits IgE-mediated passive cutaneous anaphylaxis in mice by stabilizing mast cells through modulating Ca{sup 2+} mobilization},
author = {Yuan, Meichun and Department of Physiology, Hubei University of Medicine, Shiyan and Li, Jianjie and Lv, Jingzhang and Mo, Xucheng and Yang, Chengbin and Chen, Xiangdong and Liu, Zhigang and Liu, Jie, E-mail: ljljz@yahoo.com},
abstractNote = {Mast cells play a key role in the pathogenesis of asthma and are a promising target for therapeutic intervention in asthma. This study investigated the effects of polydatin (PD), a resveratrol glucoside, on mast cell degranulation upon cross-linking of the high-affinity IgE receptors (FcεRI), as well as the anti-allergic activity of PD in vivo. Herein, we demonstrated that PD treatment for 30 min suppressed FcεRI-mediated mast cell degranulation in a dose-dependent manner. Concomitantly, PD significantly decreased FcεRI-mediated Ca{sup 2+} increase in mast cells. The suppressive effects of PD on FcεRI-mediated Ca{sup 2+} increase were largely inhibited by using LaCl{sub 3} to block the Ca{sup 2+} release-activated Ca{sup 2+} channels (CRACs). Furthermore, PD significantly inhibited Ca{sup 2+} entry through CRACs evoked by thapsigargin (TG). Knocking down protein expression of Orai1, the pore-forming subunit of CRACs, significantly decreased PD suppression of FcεRI-induced intracellular Ca{sup 2+} influx and mast cell degranulation. In a mouse model of mast cell-dependent passive cutaneous anaphylaxis (PCA), in vivo PD administration suppressed mast cell degranulation and inhibited anaphylaxis. Taken together, our data indicate that PD stabilizes mast cells by suppressing FcεRI-induced Ca{sup 2+} mobilization mainly through inhibiting Ca{sup 2+} entry via CRACs, thus exerting a protective effect against PCA. -- Highlights: ► Polydatin can prevent the pathogenesis of passive cutaneous anaphylaxis in mice. ► Polydatin stabilizes mast cells by decreasing FcεRI-mediated degranulation. ► Polydatin suppresses Ca{sup 2+} entry through CRAC channels in mast cells.},
doi = {10.1016/J.TAAP.2012.08.024},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 264,
place = {United States},
year = {2012},
month = {11}
}