Activation of the Transcription Factor FosB/Activating Protein-1 (AP-1) Is a Prominent Downstream Signal of the Extracellular Nucleotide Receptor P2RX7 in Monocytic and Osteoblastic Cells

Monica L. Gavala; Lindsay Hill; Lisa Y. Lenertz; Maya R. Karta; Paul Bertics

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Activation of the Transcription Factor FosB/Activating Protein-1 (AP-1) Is a Prominent Downstream Signal of the Extracellular Nucleotide Receptor P2RX7 in Monocytic and Osteoblastic Cells

机译：转录因子FOSB /活化蛋白-1（AP-1）的激活是单核细胞和骨细胞细胞中细胞外核苷酸受体P2RX7的突出下游信号

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Activation of the ionotropic P2RX7 nucleotide receptor by extracellular ATP has been implicated in modulating inflammatory disease progression. Continuous exposure of P2RX7 to ligand can result in apoptosis in many cell types, including monocytic cells, whereas transient activation of P2RX7 is linked to inflammatory mediator production and the promotion of cell growth. Given the rapid hydrolysis of ATP in the circulation and interstitial space, transient activation of P2RX7 appears critically important for its action, yet its effects on gene expression are unclear. The present study demonstrates that short-term stimulation of human and mouse monocytic cells as well as mouse osteoblasts with P2RX7 agonists substantially induces the expression of several activating protein-1 (AP-1) members, particularly FosB. The potent activation of FosB after P2RX7 stimulation is especially noteworthy considering that little is known concerning the role of FosB in immunological regulation. Interestingly, the magnitude of FosB activation induced by P2RX7 stimulation appears greater than that observed with other known inducers of FosB expression. In addition, we have identified a previously unrecognized role for FosB in osteoblasts with respect to nucleotide-induced expression of cyclooxygenase-2 (COX-2), which is the rate-limiting enzyme in prostaglandin biosynthesis from arachidonic acid and is critical for osteoblastic differentiation and immune behavior. The present studies are the first to link P2RX7 action to FosB/AP-1 regulation in multiple cell types, including a role in nucleotide-induced COX-2 expression, and support a role for FosB in the control of immune and osteogenic function by P2RX7.

机译：通过细胞外ATP激活离子孔P2RX7核苷酸受体对调节炎症性疾病进展有影响。 P2RX7对配体的连续暴露可以在许多细胞类型中导致细胞凋亡，包括单核细胞，而P2RX7的瞬态激活与炎症介质的产生和细胞生长的促进相关。鉴于循环和间隙空间中ATP的快速水解，P2RX7的瞬态激活对于其作用来说至关重要，但其对基因表达的影响尚不清楚。本研究表明，具有P2RX7激动剂的人和小鼠单核细胞的短期刺激以及小鼠骨细胞基本上诱导几种活化蛋白-1（AP-1）构件，特别是FOSB的表达。 P2RX7刺激后FOSB的有效活化尤其值得注意，考虑到众所周知的是FOSB在免疫调节中的作用。有趣的是，P2RX7刺激诱导的FOSB活化的大小看起来大于用其他已知的FOSB表达诱导剂观察到的。此外，我们已经确定了对核苷酸诱导的环氧化酶-2（COX-2）的核苷酸诱导的表达的核细胞中以前未被识别的作用，这是来自植物酸的前列腺素生物合成的速率限制酶，对于骨细胞分化至关重要和免疫行为。本研究是首先将P2RX7在多种细胞类型中链接到FOSB / AP-1调节的P2RX7作用，包括在核苷酸诱导的COX-2表达中的作用，并支持FOSB在通过P2RX7控制免疫和骨代函数中的作用。

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《The Journal of biological chemistry》 |2010年第2010期|共11页
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Monica L. Gavala; Lindsay Hill; Lisa Y. Lenertz; Maya R. Karta; Paul Bertics;
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AP-1 Transcription FactorATPCyclooxygenase (COX) PathwayFosInnate ImmunityPurinergic AgonistsPurinergic ReceptorSignal TransductionMonocytic CellsOsteoblasts;

机译：AP-1转录因子酸盐（COX）途径呋喃氨酸免疫性纯嘌呤肾上腺素能纯剂受体转药纯细胞蛋白;

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1. Epicatechin induces NF- kappa B, activator protein-1 (AP-1) and nuclear transcription factor erythroid 2p45-related factor-2 (Nrf2) via phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and extracellular regulated kinase (ERK) signalling inHepG2 cells. [J] . Granado-Serrano A. B., Martin M. A., Haegeman G., The British Journal of Nutrition . 2010,第2期

机译：表儿茶素通过磷脂酰肌醇3激酶/蛋白激酶B（PI3K / AKT）和细胞外调节激酶（NF-κB，活化蛋白1（AP-1）和核转录因子红细胞2p45相关因子2（Nrf2）诱导。 ERK）在HepG2细胞中发出信号。
2. Epicatechin induces NF- kappaB, activator protein-1 (AP-1) and nuclear transcription factor erythroid 2p45-related factor-2 (Nrf2) via phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and extracellular regulated kinase (ERK) signalling inHepG2 cells. [J] . Granado-Serrano A. B., Martin M. A., Haegeman G., The British Journal of Nutrition . 2010,第2期

机译：表儿茶素通过磷脂酰肌醇3激酶/蛋白激酶B（PI3K / AKT）和细胞外调节激酶（ERK）诱导NF-κB，激活蛋白1（AP-1）和核转录因子红细胞2p45相关因子2（Nrf2）。）在HeepG2细胞中发出信号。
3. Epicatechin induces NF-κB, activator protein-1 (AP-1) and nuclear transcription factor erythroid 2p45-related factor-2 (Nrf2) via phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and extracellular regulated kinase (ERK) signalling in HepG2 cells [J] . Ana Belén Granado-Serrano, Guy Haegeman, Laura Bravo, The British Journal of Nutrition . 2009,第2期

机译：表儿茶素通过磷脂酰肌醇3激酶/蛋白激酶B（PI3K / AKT）和细胞外调节激酶（ERK）诱导NF-κB，激活蛋白1（AP-1）和核转录因子红细胞2p45相关因子2（Nrf2）。）在HepG2细胞中的信号转导
4. CCK-B receptor activation in human lymphoblastic Jurkat cells results in AP-1 responsive genes activation [C] . D.Gagne, N.Bernad, C.Oiry, Chinese peptide symposium . 1998

机译：CCK-B受体激活人淋巴细胞julkat细胞导致AP-1响应基因活化
5. Regulation of the progesterone receptor in the mouse mammary gland: Characterization of the transcription unit, the role of activating protein-1 (AP-1), and the influence of ovarian hormones. [D] . Flynn, Emily Elizabeth. 2011

机译：小鼠乳腺中孕激素受体的调节：转录单位的表征，激活蛋白1（AP-1）的作用以及卵巢激素的影响。
6. Activation of the Transcription Factor FosB/Activating Protein-1 (AP-1) Is a Prominent Downstream Signal of the Extracellular Nucleotide Receptor P2RX7 in Monocytic and Osteoblastic Cells [O] . Monica L. Gavala, Lindsay M. Hill, Lisa Y. Lenertz, 2010

机译：转录因子FosB /激活蛋白-1（AP-1）的激活是单核细胞和成骨细胞中细胞外核苷酸受体P2RX7的明显下游信号。
7. Activation of the Transcription Factor FosB/Activating Protein-1 (AP-1) Is a Prominent Downstream Signal of the Extracellular Nucleotide Receptor P2RX7 in Monocytic and Osteoblastic Cells* [O] . Gavala, Monica L., Hill, Lindsay M., Lenertz, Lisa Y., 2010

机译：转录因子FosB /活化蛋白1（AP-1）的激活是单核细胞和成骨细胞中细胞外核苷酸受体P2RX7的明显下游信号*

Activation of the Transcription Factor FosB/Activating Protein-1 (AP-1) Is a Prominent Downstream Signal of the Extracellular Nucleotide Receptor P2RX7 in Monocytic and Osteoblastic Cells

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