TY - JOUR
T1 - Saikosaponin A inhibits compound 48/80-induced pseudo-allergy via the Mrgprx2 pathway in vitro and in vivo
AU - Wang, Nan
AU - Che, Delu
AU - Zhang, Tao
AU - Liu, Rui
AU - Cao, Jiao
AU - Wang, Jue
AU - Zhao, Tingting
AU - Ma, Pengyu
AU - Dong, Xinzhong
AU - He, Langchong
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China (Grant Number: 81230079 , 81227802 and 81503321 ), China Postdoctoral Science Foundation (Grant Number: 2016M592808 ) and Natural Science Foundation of Shaanxi Province (Grant Number: 2016JQ8025 ).
Publisher Copyright:
© 2017 Elsevier Inc.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2018/2
Y1 - 2018/2
N2 - Pseudo-allergic reactions-adverse, non-immunologic, anaphylaxis-like sudden onset reactions mediated through an IgE-independent pathway—are activated by various basic compounds and occur at least as frequently as IgE-mediated reactions to drugs. A large family of G protein coupled receptors (Mas-related genes; Mrgprs) is closely related to pseudo-allergies. However, few therapies can directly target pseudo-allergies and related Mrgprs. Saikosaponin A (SSA) is effective in the treatment of passive cutaneous anaphylaxis (PCA), adjuvant arthritis, and delayed hypersensitiveness. In this study, we investigated the anti-pseudo-allergy effect of SSA and its underlying mechanism. We examined the effect of SSA on both IgE-independent and IgE-dependent responses using PCA and active systemic anaphylaxis models, as well as in vitro-cultured mast cells. We also evaluated whether the anti-allergy effect is related to Mrgprs by using in vitro Mrgprx2-expressing HEK293 cells. SSA dose dependently suppressed compound 48/80 (C48/80)-induced PCA and mast cell degranulation in mice. When SSA and C48/80 were administered together through the vein, C48/80-induced systemic anaphylaxis did not occur, and C48/80-induced shock ratio decreased dose-dependently upon SSA treatment. However, SSA did not affect IgE-dependent allergy. When administered topically 24 h before antigen challenge, Evans blue leakage and paw swelling were induced in the SSA-treated group and the vehicle group. Our in vitro studies revealed that SSA reduced C48/80-induced calcium flux and suppressed degranulation in LAD2 cells. SSA could also dose-dependently inhibit C48/80-induced Mrgprx2-expressing HEK293 cell activation. As a conclusion, SSA could inhibits IgE-independent allergy, but not IgE-dependent allergy, and this effect involves the Mrgprx2 pathway. This study provided a new sight on pseudo-allergy and its therapy.
AB - Pseudo-allergic reactions-adverse, non-immunologic, anaphylaxis-like sudden onset reactions mediated through an IgE-independent pathway—are activated by various basic compounds and occur at least as frequently as IgE-mediated reactions to drugs. A large family of G protein coupled receptors (Mas-related genes; Mrgprs) is closely related to pseudo-allergies. However, few therapies can directly target pseudo-allergies and related Mrgprs. Saikosaponin A (SSA) is effective in the treatment of passive cutaneous anaphylaxis (PCA), adjuvant arthritis, and delayed hypersensitiveness. In this study, we investigated the anti-pseudo-allergy effect of SSA and its underlying mechanism. We examined the effect of SSA on both IgE-independent and IgE-dependent responses using PCA and active systemic anaphylaxis models, as well as in vitro-cultured mast cells. We also evaluated whether the anti-allergy effect is related to Mrgprs by using in vitro Mrgprx2-expressing HEK293 cells. SSA dose dependently suppressed compound 48/80 (C48/80)-induced PCA and mast cell degranulation in mice. When SSA and C48/80 were administered together through the vein, C48/80-induced systemic anaphylaxis did not occur, and C48/80-induced shock ratio decreased dose-dependently upon SSA treatment. However, SSA did not affect IgE-dependent allergy. When administered topically 24 h before antigen challenge, Evans blue leakage and paw swelling were induced in the SSA-treated group and the vehicle group. Our in vitro studies revealed that SSA reduced C48/80-induced calcium flux and suppressed degranulation in LAD2 cells. SSA could also dose-dependently inhibit C48/80-induced Mrgprx2-expressing HEK293 cell activation. As a conclusion, SSA could inhibits IgE-independent allergy, but not IgE-dependent allergy, and this effect involves the Mrgprx2 pathway. This study provided a new sight on pseudo-allergy and its therapy.
KW - IgE-independent
KW - Mast cells
KW - Mrgprx2
KW - Pseudo-allergy
KW - Saikosaponin A
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UR - http://www.scopus.com/inward/citedby.url?scp=85040231018&partnerID=8YFLogxK
U2 - 10.1016/j.bcp.2017.12.017
DO - 10.1016/j.bcp.2017.12.017
M3 - Article
C2 - 29274317
AN - SCOPUS:85040231018
SN - 0006-2952
VL - 148
SP - 147
EP - 154
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
ER -