Mouse pyrin and HIN domain family member 1 (pyhin1) protein positively regulates LPS-induced IFN-β and NO production in macrophages
Mouse pyrin and HIN domain family member 1 (pyhin1) protein positively regulates LPS-induced IFN-β and NO production in macrophages
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DOI：
10.1177/1753425913481636
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发表时间：
2014-01-01
期刊：
影响因子：
3.2
通讯作者：
Yokochi, Takashi
中科院分区：
文献类型：
--
作者：
Haque, Abedul;Koide, Naoki;Yokochi, Takashi
Pyrin 和 HIN 结构域 (PYHIN) 家族成员 1 (pyhin1) 是 PYHIN 蛋白的成员，参与对细胞周期控制、分化和凋亡至关重要的基因的转录调控。研究了小鼠 pyhin1 对 LPS 诱导的炎症反应的调节作用。 LPS 增强了小鼠 RAW 264.7 巨噬细胞和腹膜巨噬细胞中 pyhin1 mRNA 的表达。 pyhin1 mRNA 表达的增强被 NF-B 抑制剂小白菊内酯消除。用小干扰 RNA 沉默 pyhin1 可减少 IFN- 和 NO 的产生。然而，pyhin1 沉默并不影响 TNF-、IL-6、IL-10 和前列腺素 E2 的产生。 pyhin1 沉默导致 IFN-产生减少，导致 STAT1 失活并减少 IRF1 表达。 Pyhin1 沉默抑制 TRAF6、TBK1 和 TRIF 的表达，从而触发 MyD88 独立途径中的 IFN-产生。然而，pyhin1 沉默并不影响 MyD88、IRAK4 和 MyD88 依赖性途径中几种丝裂原激活蛋白激酶的表达。综上所述，小鼠 pyhin1 被认为是响应 LPS 的 NF-B 响应基因，并通过上调 MyD88 独立信号通路来正向调节 LPS 诱导的 IFN 和 NO 产生。
The pyrin and HIN-domain (PYHIN) family member1 (pyhin1) is a member of PYHIN proteins and involved in transcriptional regulation of genes important for cell cycle control, differentiation and apoptosis. The regulatory action of mouse pyhin1 on LPS-induced inflammatory response was examined. LPS augmented the pyhin1 mRNA expression in murine RAW 264.7 macrophage cells and peritoneal macrophages. The augmentation of pyhin1 mRNA expression was abolished by parthenolide, a NF-B inhibitor. Silencing of pyhin1 with small interfering RNA reduced the production of IFN- and NO. However, pyhin1 silencing did not affect the production of TNF-, IL-6, IL-10 and prostaglandin E2. Reduced IFN- production by pyhin1 silencing caused inactivation of STAT1 and reduced expression of IRF1. Pyhin1 silencing inhibited the expression of TRAF6, TBK1 and TRIF, which trigger IFN- production in the MyD88-independent pathway. However, pyhin1 silencing did not affect the expression of MyD88, IRAK4 and several mitogen-activated protein kinases in the MyD88-dependent pathway. Taken together, mouse pyhin1 was suggested to be a NF-B-responsible gene in response to LPS and positively regulate LPS-induced IFN- and NO production through up-regulating the MyD88-independent signaling pathway.