1. Secreted phosphoprotein 1 regulates natural compound 3',4',5,7-tetrahydroxyflavone to inhibit mast cell-mediated allergic inflammation.
- Author
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Shiling Hu, Jue Wang, Haoyun Bai, Chaohua Feng, Zhenqi Zhou, Zhuoyin Xue, Wen Zhang, Yongjing Zhang, Nan Wang, and Langchong He
- Subjects
TRYPTASE ,MAST cells ,CULTIVARS ,CALCIUM ions ,HISTAMINE ,INFLAMMATION ,KOUNIS syndrome - Abstract
Background: Mast cells (MCs) are important effector cells in anaphylaxis and anaphylactic disease. 3',4',5,7-tetrahydroxyflavone (THF) presents in many medicinal plants and exerts a variety of pharmacological effects. In this study, we evaluated the effect of THF on C48/80-induced anaphylaxis and the mechanisms underlying its effects, including the role of secreted phosphoprotein 1 (SPP1), which has not been reported to IgE-independent MC activation. Results: THF inhibited C48/80-induced Ca2+ flow and degranulation via the PLC/PKC/IP3 pathway in vitro. RNA-seq showed that THF inhibited the expression of SPP1 and downstream molecules. SPP1 is involved in pseudo-anaphylaxis reactions. Silencing SPP1 affects the phosphorylation of AKT and P38. THF suppressed C48/80-induced paw edema, hypothermia and serum histamine, and chemokines release in vivo. Conclusions: Our results validated SPP1 is involved in IgE-independent MC activation anaphylactoid reactions. THF inhibited C48/80-mediated anaphylactoid reactions both in vivo and in vitro, suppressed calcium mobilization and inhibited SPP1-related pathways. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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