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

• Published in: International journal of immunopathology and pharmacology Vol. 29; no. 4; pp. 676 - 683
• Main Authors: Wang, Nan, Liu, Rui, Liu, Yanping, Zhang, Ruirui, He, Langchong
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.12.2016; Sage Publications Ltd
• Subjects: Allergies; Anaphylaxis; Anaphylaxis - drug therapy; Anaphylaxis - metabolism; Animals; Anti-Allergic Agents - pharmacology; Anti-Inflammatory Agents - pharmacology; Calcium (reticular); Calcium - metabolism; Calcium mobilization; Cell activation; Cell Degranulation - drug effects; Cell Line, Tumor; Degranulation; Drug Hypersensitivity - drug therapy; Drug Hypersensitivity - metabolism; Endoplasmic reticulum; Enzyme-linked immunosorbent assay; Histamine; Inflammation - drug therapy; Inflammation - metabolism; Inositol 1,4,5-trisphosphate receptors; Inositol 1,4,5-Trisphosphate Receptors - metabolism; Interleukin-6 - metabolism; Intravenous administration; Male; Mast cells; Mast Cells - drug effects; Mast Cells - metabolism; Mice; Mice, Inbred BALB C; Morphinans - pharmacology; Original; Phospholipase C; Phospholipase C gamma - metabolism; Phosphorylation; Phosphorylation - drug effects; Sarcoma; Signal Transduction - drug effects; Sinomenium acutum; src-Family Kinases - metabolism; Up-Regulation - drug effects; sinomenine; anaphylaxis; degranulation
• ISSN: 2058-7384; 0394-6320; 2058-7384
• DOI: 10.1177/0394632015621768

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.