Sinomenine potentiates P815 cell degranulation via upregulation of Ca2+ mobilization through the Lyn/PLCγ/IP3R pathway.

Abstract:

:Mast cells are vital mediators of drug allergy and, therefore, studying the relationship between drug allergy and mast cells is essential. Sinomenine is the principal active component of Sinomenium acutum, which has anti-inflammatory and anti-immune effects, and is used to treat various rheumatoid diseases. However, allergic responses to sinomenine are frequently reported. Therefore, this study assessed the effects of sinomenine on mast cell activation to characterize its allergic effects and the underlying mechanisms. Enzyme-linked immunosorbent assay (ELISA), western blot analyses, and degranulation assays were performed to measure pro-inflammatory and allergic mediators in P815 cells. The allergenic effects of sinomenine were also determined in mice by using active general anaphylaxis (ASA). The results indicated that sinomenine induced inositol-1,4,5-trisphosphate (IP3) production and the release of histamine, interleukin (IL)-6, and endoplasmic reticulum Ca2+ in P815 cells. Furthermore, sinomenine upregulated the phosphorylation of sarcoma (Src), phospholipase C (PLC)-γ1, and IP3 receptor (R). Therefore, sinomenine induced concentration-dependent mast cell activation directly in vitro Furthermore, our in vivo data identified an appropriate intravenous dose that did not induce these allergic effects, thereby providing information for the potential safe clinical use of sinomenine.

authors

Wang N,Liu R,Liu Y,Zhang R,He L

doi

10.1177/0394632015621768

subject

Has Abstract

pub_date

2016-12-01 00:00:00

pages

676-683

issue

4

eissn

0394-6320

issn

2058-7384

pii

0394632015621768

journal_volume

29

pub_type

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