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FOXO3a Involvement in the Release of TNF-α Stimulated by ATP in Spinal Cord Astrocytes

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Abstract

Spinal cord injury is characterized by an inflammatory response that includes the increased expression of several cytokines and chemokines. Extracellular adenosine triphosphate (ATP) acts as a critical endogenous signaling molecule in inflammation and immunity. However, the molecular and cellular mechanisms of the proinflammatory cytokines stimulated by ATP are poorly understood. Mammalian forkhead members of the class O (FOXO) are involved in a variety of signaling pathways. In this study, we have found that ATP could selectively decrease the expression of FOXO1 and FOXO3a via the phosphorylation of epidermal growth factor receptor (EGFR) and Akt in spinal cord astrocytes. However, ATP had no effect on the expression of FOXO4 and FOXO6, and EGFR, Akt, and ERK1/2 all involve in the release of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) induced by ATP. In addition, we have researched that the overexpressed FOXO3a could specially inhibit the release of TNF-α increased by ATP, but the level of IL-6 induced by ATP was not decreased. Meanwhile, there was no change in the release of IL-6 and TNF-α after FOXO1 was overexpressed. Understanding the critical role of FOXO3a in astrocytes stimulated by ATP may provide a potential target for therapeutic intervention after spinal cord injury.

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Acknowledgments

This study was supported by grant no. 81200935 to MX and grant nos. 30000167, 39870818, and 81271939 to YZ from the National Natural Science Foundation of China, grants no. 20102104120002 to MX from Doctoral Fund of Ministry of Education of China, and grant no. L2011135 to MX from Educational Commission of Liaoning Province.

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  1. Department of Orthopaedics, The First Hospital of China Medical University, No. 155 Njingbei Road, 110001, , Heping District,, Shenyang, People’s Republic of China

    Maosheng Xia & Yue Zhu

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  1. Maosheng Xia
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  2. Yue Zhu
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Correspondence to Yue Zhu.

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Xia, M., Zhu, Y. FOXO3a Involvement in the Release of TNF-α Stimulated by ATP in Spinal Cord Astrocytes. J Mol Neurosci 51, 792–804 (2013). https://doi.org/10.1007/s12031-013-0067-8

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