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首页> 外文期刊>Journal of cellular biochemistry. >Macrophage inflammatory protein-1alpha induces osteoclast formation by activation of the MEK/ERK/c-Fos pathway and inhibition of the p38MAPK/IRF-3/IFN-beta pathway.
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Macrophage inflammatory protein-1alpha induces osteoclast formation by activation of the MEK/ERK/c-Fos pathway and inhibition of the p38MAPK/IRF-3/IFN-beta pathway.

机译:巨噬细胞炎性蛋白1α通过激活MEK / ERK / c-Fos途径和抑制p38MAPK / IRF-3 /IFN-β途径诱导破骨细胞形成。

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摘要

Multiple myeloma (MM) is a bone disease that affects many individuals. It was recently reported that macrophage inflammatory protein (MIP)-1alpha is constitutively secreted by MM cells. MIP-1alpha causes bone destruction through the formation of osteoclasts (OCs). However, the molecular mechanism underlying MIP-1alpha-induced OC formation is not well understood. In the present study, we attempted to clarify the mechanism whereby MIP-1alpha induces OC formation in a mouse macrophage-like cell line comprising C7 cells. We found that MIP-1alpha augmented OC formation in a concentration-dependent manner; moreover, it inhibited IFN-beta and ISGF3gamma mRNA expression, and IFN-beta secretion. MIP-1alpha increased the expressions of phosphorylated ERK1/2 and c-Fos and decreased those of phosphorylated p38MAPK and IRF-3. We found that the MEK1/2 inhibitor U0126 inhibited OC formation by suppressing the MEK/ERK/c-Fos pathway. SB203580 induced OC formation by upregulating c-fos mRNA expression, and SB203580 was found to inhibit IFN-beta and IRF-3 mRNA expressions. The results indicate that MIP-1alpha induces OC formation by activating and inhibiting the MEK/ERK/c-Fos and p38MAPK/IRF-3 pathways, respectively, and suppressing IFN-beta expression. These findings may be useful in the development of an OC inhibitor that targets intracellular signaling factors.
机译:多发性骨髓瘤(MM)是一种影响许多个体的骨病。最近有报道说,MM细胞组成性分泌巨噬细胞炎性蛋白(MIP)-1alpha。 MIP-1alpha通过破骨细胞(OCs)的形成引起骨破坏。但是,MIP-1alpha诱导的OC形成的分子机制尚不十分清楚。在本研究中,我们试图阐明MIP-1alpha诱导包含C7细胞的小鼠巨噬细胞样细胞系中OC形成的机制。我们发现,MIP-1alpha以浓度依赖的方式增加了OC的形成。此外,它抑制了IFN-β和ISGF3gamma mRNA的表达以及IFN-β的分泌。 MIP-1alpha增加了磷酸化的ERK1 / 2和c-Fos的表达,并降低了磷酸化的p38MAPK和IRF-3的表达。我们发现MEK1 / 2抑制剂U0126通过抑制MEK / ERK / c-Fos途径抑制了OC的形成。 SB203580通过上调c-fos mRNA表达诱导OC形成,并且发现SB203580抑制IFN-beta和IRF-3 mRNA表达。结果表明,MIP-1alpha分别通过激活和抑制MEK / ERK / c-Fos和p38MAPK / IRF-3途径并抑制IFN-β表达来诱导OC形成。这些发现可能对开发靶向细胞内信号转导因子的OC抑制剂有用。

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