title: FOXO3a involvement in the release of TNF-α stimulated by ATP in spinal cord astrocytes.
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.
authors.affiliation: Department of Orthopaedics, The First Hospital of China Medical University, No. 155 Njingbei Road, 110001, , Heping District,, Shenyang, People's Republic of China.
authors.forename: Maosheng
authors.initials: M
authors.lastname: Xia
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; C467200:Foxo1 protein, mouse; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000255:Adenosine Triphosphate; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases