Prostaglandin E2 induces interleukin-8 gene transcription by activating C/EBP homologous protein in human T lymphocytes
Prostaglandin E2 induces interleukin-8 gene transcription by activating C/EBP homologous protein in human T lymphocytes
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DOI：
10.1074/jbc.m410725200
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发表时间：
2005-04-15
影响因子：
4.8
通讯作者：
Teti, D
中科院分区：
文献类型：
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作者：
Caristi, S;Piraino, G;Teti, D
前列腺素 E-2 (PGE(2)) 在调节 T 淋巴细胞中促炎趋化因子白细胞介素 8 (IL-8) 合成方面的作用尚未确定，尽管它可能会减少或增强其他细胞类型中 IL-8 的合成。在这里，我们证明，在人类 T 细胞中，PGE(2) 通过前列腺素 E-2 受体 1 和 4 依赖性信号转导途径诱导 IL-8 mRNA 转录，从而导致转录因子 C/EBP 同源蛋白 (CHOP) 的激活，这在之前从未涉及过 IL-8 转录。多种激酶，包括蛋白激酶 C、Src 家族酪氨酸激酶、磷脂酰肌醇 3-激酶和 p38 MAPK，参与 PGE(2) 诱导的 CHOP 激活和 IL-8 产生。 CHOP 对 IL-8 启动子的反式激活不依赖于 NF-κ B。我们的数据表明，PGE(2) 通过不同的信号转导途径诱导活化的 T 细胞中 IL-8 基因转录，从而导致 CHOP 激活，从而充当有效的促炎介质。这些发现表明，PGE(2) 通过根据细胞类型和环境条件抑制或增强 IL-8 的产生来调节 IL-8 合成的复杂性。
The effect of prostaglandin E-2 (PGE(2)) in regulating the synthesis of the pro-inflammatory chemokine interleukin-8 (IL-8) in T lymphocytes is not yet defined, even though it may reduce or enhance IL-8 synthesis in other cell types. Here, we demonstrate that, in human T cells, PGE(2) induced IL-8 mRNA transcription through prostaglandin E-2 receptors 1- and 4-dependent signal transduction pathways leading to the activation of the transcription factor C/EBP homologous protein ( CHOP), never before implicated in IL-8 transcription. Several kinases, including protein kinase C, Src family tyrosine kinases, phosphatidylinositol 3-kinase, and p38 MAPK, were involved in PGE(2)-induced CHOP activation and IL-8 production. The transactivation of the IL-8 promoter by CHOP was NF-kappa B-independent. Our data suggest that PGE(2) acts as a potent pro-inflammatory mediator by inducing IL-8 gene transcription in activated T cells through different signal transduction pathways leading to CHOP activation. These findings show the complexity with which PGE(2) regulates IL-8 synthesis by inhibiting or enhancing its production depending on the cell types and environmental conditions.