Suppressive role of PPARγ in the IgE-dependent activation of mast cells.
Suppressive role of PPARγ in the IgE-dependent activation of mast cells.
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PPARγ 在 IgE 依赖性肥大细胞激活中的抑制作用。
DOI：
10.1093/intimm/dxz069
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发表时间：
2020
影响因子：
4.4
通讯作者：
Nishiyama C.
中科院分区：
文献类型：
--
作者：
Nagata K;Kasakura K;Miura R;Yashiro T;Nishiyama C.
肥大细胞（MC）在IgE依赖性免疫应答中起核心作用。过氧化物酶体增殖物激活受体γ是一种核受体，对脂肪细胞分化和胰岛素敏感性至关重要。尽管PPARγ在活化的MC中表达，但在IgE介导的MC活化中抑制PPARγ的作用在很大程度上是未知的。在本研究中，我们使用siRNA转染的骨髓来源的MCs（BMMCs）评估了PPARγ敲低对IgE+抗原（Ag）刺激的MCs功能的影响。结果发现，在PPARγ基因敲低的BMMCs中，IgE/Ag刺激的BMMCs细胞因子的mRNA表达水平显著升高，而细胞表面FcεRI的表达水平不受PPARγ基因敲低的影响。口服吡格列酮（PPARγ激动剂）可显著抑制被动全身过敏反应小鼠的体温变化，支持了PPARγ在体内抑制IgE/Ag依赖的MC活化的功能。IgE介导的Ptgs 2（编码考克斯-2）mRNA水平的上调在PPARγ敲低的BMMCs中显著增强。尽管已知几种前列腺素（PG）衍生物是PPARγ的配体，但用考克斯抑制剂乙酰水杨酸处理，与PPARγ siRNA协同上调IgE介导的IL 13、Tnf和Ptgs 2 mRNA水平的增加。通过siRNA敲低考克斯-1和/或考克斯-2表明，抑制IgE/Ag介导的活化主要依赖于考克斯-1。综上所述，这些结果表明，PPARγ抑制IgE/Ag诱导的细胞因子基因和MCs中Ptgs 2基因的反式激活的方式与PGs不同。
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 MCsin vivo. IgE-mediated up-regulation of mRNA levels ofPtgs2(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 ofIl13,TnfandPtgs2mRNA 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 thePtgs2gene in MCs in a manner distinguishable from that of PGs.
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PPARα/γ 配体对肥大细胞中半胱氨酰白三烯产生的 PPARα/γ 独立影响
影响因子：
2.9
作者：
M. Yamashita
通讯作者：
M. Yamashita
影响因子：
7.3
作者：
Heming M;Gran S;Jauch SL;Fischer-Riepe L;Russo A;Klotz L;Hermann S;Schäfers M;Roth J;Barczyk-Kahlert K
通讯作者：
Barczyk-Kahlert K
影响因子：
7.3
作者：
Nieto C;Bragado R;Municio C;Sierra-Filardi E;Alonso B;Escribese MM;Domínguez-Andrés J;Ardavín C;Castrillo A;Vega MA;Puig-Kröger A;Corbí AL
通讯作者：
Corbí AL
影响因子：
82.9
作者：
Y. Shimanaka;N. Kono;Y. Taketomi;M. Arita;Y. Okayama;Yuki Tanaka;Y. Nishito;Tatsuki Mochizuki;H. Kusuhara;A. Adibekian;B. Cravatt;M. Murakami;H. Arai
通讯作者：
Y. Shimanaka;N. Kono;Y. Taketomi;M. Arita;Y. Okayama;Yuki Tanaka;Y. Nishito;Tatsuki Mochizuki;H. Kusuhara;A. Adibekian;B. Cravatt;M. Murakami;H. Arai
影响因子：
15.9
作者：
Shan, Ming;You, Ran;Kheradmand, Farrah
通讯作者：
Kheradmand, Farrah