Secreted phosphoprotein 1 regulates natural compound 3',4',5,7-tetrahydroxyflavone to inhibit mast cell-mediated allergic inflammation.

IF 2.9 4区医学 Q3 IMMUNOLOGY Immunopharmacology and Immunotoxicology Pub Date : 2023-12-01 Epub Date: 2023-07-03 DOI:10.1080/08923973.2023.2228478

Shiling Hu, Jue Wang, Haoyun Bai, Chaohua Feng, Zhenqi Zhou, Zhuoyin Xue, Wen Zhang, Yongjing Zhang, Nan Wang, Langchong He

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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 PLCγ/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.

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分泌磷酸化蛋白1调节天然化合物3'，4'，5,7-四羟黄酮抑制肥大细胞介导的过敏性炎症。

背景:肥大细胞(MCs)是过敏反应和过敏性疾病的重要效应细胞。3'，4'，5,7-四羟黄酮(THF)存在于许多药用植物中，具有多种药理作用。在这项研究中，我们评估了THF对c48 /80诱导的过敏反应的影响及其作用机制，包括分泌磷酸化蛋白1 (SPP1)的作用，SPP1尚未被报道与ige无关的MC激活。结果:THF在体外通过PLCγ/PKC/IP3途径抑制c48 /80诱导的Ca2+流动和脱粒。RNA-seq结果显示，THF抑制SPP1及其下游分子的表达。SPP1参与假性过敏反应。沉默SPP1会影响AKT和P38的磷酸化。THF在体内抑制c48 /80诱导的足跖水肿、低温、血清组胺和趋化因子释放。结论:我们的研究结果证实SPP1参与了不依赖ige的MC激活类过敏反应。THF在体内和体外均能抑制c48 /80介导的类过敏反应，抑制钙动员，抑制spp1相关通路。

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来源期刊

Immunopharmacology and Immunotoxicology 医学-毒理学

CiteScore

5.40

自引率

0.00%

发文量

133

审稿时长

4-8 weeks

期刊介绍： The journal Immunopharmacology and Immunotoxicology is devoted to pre-clinical and clinical drug discovery and development targeting the immune system. Research related to the immunoregulatory effects of various compounds, including small-molecule drugs and biologics, on immunocompetent cells and immune responses, as well as the immunotoxicity exerted by xenobiotics and drugs. Only research that describe the mechanisms of specific compounds (not extracts) is of interest to the journal. The journal will prioritise preclinical and clinical studies on immunotherapy of disorders such as chronic inflammation, allergy, autoimmunity, cancer etc. The effects of small-drugs, vaccines and biologics against central immunological targets as well as cell-based therapy, including dendritic cell therapy, T cell adoptive transfer and stem cell therapy, are topics of particular interest. Publications pointing towards potential new drug targets within the immune system or novel technology for immunopharmacological drug development are also welcome. With an immunoscience focus on drug development, immunotherapy and toxicology, the journal will cover areas such as infection, allergy, inflammation, tumor immunology, degenerative disorders, immunodeficiencies, neurology, atherosclerosis and more. Immunopharmacology and Immunotoxicology will accept original manuscripts, brief communications, commentaries, mini-reviews, reviews, clinical trials and clinical cases, on the condition that the results reported are based on original, clinical, or basic research that has not been published elsewhere in any journal in any language (except in abstract form relating to paper communicated to scientific meetings and symposiums).