Down-regulation of tristetraprolin expression results in enhanced IL-12 and MIP-2 production and reduced MIP-3alpha synthesis in activated macrophages.
Down-regulation of tristetraprolin expression results in enhanced IL-12 and MIP-2 production and reduced MIP-3alpha synthesis in activated macrophages.
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DOI：
10.1155/mi/2006/40691
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发表时间：
2006
影响因子：
4.6
通讯作者：
Moilanen E
中科院分区：
文献类型：
--
作者：
Jalonen U;Nieminen R;Vuolteenaho K;Kankaanranta H;Moilanen E
在炎症中，瞬时表达基因的转录后调控提供了一个潜在的治疗靶点。三戊三酚（TTP）是调节细胞因子mrna衰变的因子之一。本研究的目的是确定表达受TTP调节的细胞因子。我们通过对TTP表达shRNA，建立了TTP敲除细胞株（shTTP细胞株）。细胞因子抗体阵列用于测量暴露于脂多糖（LPS）的巨噬细胞中细胞因子的产生。在lps处理的shTTP细胞中，细胞因子IL-6、IL-12、TNF-α和MIP-2（与人IL-8同源）的表达水平较高，而MIP-3α的表达水平较低，表明这些细胞因子的表达受TTP调节。目前的数据表明，IL-12、MIP-2和MIP-3α是TTP介导的mRNA衰变的新炎症细胞因子靶点，并强调了TTP在炎症过程中的调节作用。
In inflammation, the post-transcriptional regulation of transiently expressed genes provides a potential therapeutic target. Tristetraprolin (TTP) is of the factors regulating decay of cytokine mRNAs. The aim of the present study was to identify cytokines whose expression is regulated by TTP. We established a TTP knock-down cell line by expressing shRNA against TTP (shTTP cell line). A cytokine antibody array was used to measure cytokine production in macrophages exposed to lipopolysaccharide (LPS). Cytokines IL-6, IL-12, TNF-α, and MIP-2 (a homologue to human IL-8) were expressed at higher levels whereas MIP-3α was produced at lower levels in LPS-treated shTTP cells than in control cells suggesting that the expression of these cytokines is regulated by TTP. The present data provide IL-12, MIP-2, and MIP-3α as novel inflammatory cytokine targets for TTP-mediated mRNA decay and stress the role of TTP in the regulation of the inflammatory process.