Mast cells (MCs) play a central role in IgE-dependent immune responses. PPARγ is a nuclear receptor that is essential for adipocyte differentiation and insulin sensitivity. Although PPARγ is expressed in activated MCs, the effect of PPARγ suppression in IgE-mediated activation of MCs is largely unknown. In the current study, we evaluated the effect of PPARγ knockdown on the function of IgE plus antigen (Ag)-stimulated MCs using siRNA-transfected bone marrow-derived MCs (BMMCs). We found that the mRNA expression level of cytokines in IgE/Ag-stimulated BMMCs was significantly increased in PPARγ knockdown BMMCs, and IgE/Ag-mediated degranulation and the protein production level of TNF-α was moderately increased by PPARγ knockdown, whereas the cell surface expression level of FcεRI was not affected by PPARγ knockdown. Oral administration of pioglitazone (PPARγ agonist) significantly suppressed body temperature change of mice in passive systemic anaphylaxis, supporting the inhibitory functions of PPARγ in IgE/Ag-dependent activation of MCs in vivo. IgE-mediated up-regulation of mRNA levels of Ptgs2 (encoding COX-2) was drastically enhanced in PPARγ knockdown BMMCs. Although several prostaglandin (PG) derivatives are known to be ligands for PPARγ, treatment with a COX inhibitor, acetyl salicylic acid, up-regulated the IgE-mediated increase of Il13, Tnf and Ptgs2 mRNA levels in a synergistic manner with PPARγ siRNA. Knockdown of COX-1 and/or COX-2 by siRNA showed that suppression of IgE/Ag-mediated activation was mainly dependent on COX-1. Taken together, these results indicate that PPARγ suppresses IgE/Ag-induced transactivation of cytokine genes and the Ptgs2 gene in MCs in a manner distinguishable from that of PGs.

中文翻译：

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PPARγ在肥大细胞IgE依赖性激活中的抑制作用。

肥大细胞（MCs）在依赖IgE的免疫反应中发挥重要作用。PPARγ是核细胞受体，对脂肪细胞的分化和胰岛素敏感性至关重要。尽管PPARγ在激活的MCs中表达，但在IgE介导的MCs激活中抑制PPARγ的作用尚不清楚。在当前的研究中，我们评估了PPARγ敲低对使用siRNA转染的骨髓MC（BMMC）对IgE加抗原（Ag）刺激的MC的功能的影响。我们发现，在PPARγ敲低的BMMC中，IgE / Ag刺激的BMMC中细胞因子的mRNA表达水平显着增加，而通过PPARγ敲低，IgE / Ag介导的脱粒和TNF-α的蛋白产生水平适度增加，而细胞FcεRI的表面表达水平不受PPARγ敲低的影响。口服吡格列酮（PPARγ激动剂）可显着抑制被动性全身过敏反应中小鼠的体温变化，从而支持PPARγ在体内对IgE / Ag依赖性MC激活的抑制功能。IgE介导的Ptgs2 mRNA水平（编码COX-2）的上调在PPARγ抑制型BMMC中得到了显着增强。尽管已知几种前列腺素（PG）衍生物是PPARγ的配体，但用COX抑制剂乙酰水杨酸处理可以与PPARγsiRNA协同作用上调IgE介导的Il13，Tnf和Ptgs2 mRNA水平的升高。siRNA敲低COX-1和/或COX-2表明，抑制IgE / Ag介导的激活主要取决于COX-1。在一起