Interleukin‐10 provides direct trophic support to neurons

Journal of Neurochemistry - Tập 110 Số 5 - Trang 1617-1627 - 2009
Zixuan Zhou1, Xiangmin Peng2, Ryan Insolera1, David J. Fink1, Marina Mata1
1Department of Neurology, University of Michigan and Ann Arbor VA Healthcare System, Ann Arbor, Michigan, USA
2UNIVERSITY OF MICHIGAN

Tóm tắt

AbstractInterleukin (IL)‐10, a prototypical anti‐inflammatory cytokine, has been shown to provide beneficial effects in neuronal injuryin vivobut the full range of actions has not been established. In order to understand the neuronal mechanisms underlying IL‐10‐mediated neuroprotection, we examined the effect of IL‐10 on primary neurons in culture. We found that IL‐10 exerted a direct trophic influence on spinal cord neurons, and that activation of the neuronal IL‐10 receptor provided trophic support and survival cues to overcome the neurotoxic effects of glutamatein vitro. IL‐10 treatment resulted in activation of janus‐associated kinases/signal transducers and transcription factors and phosphatidylinositol 3‐kinase‐AKT pathways in neurons to enhance expression of Bcl‐2 and Bcl‐xL; under stress conditions IL‐10 blocks cytochromecrelease and caspase cleavage. IL‐10 activation of the canonical nuclear factor κB pathway enhanced translocation of p50 and p65 and enhanced their binding to κB DNA sequences, with p50 playing a more prominent role in neuronal survival. These data indicate that in addition to known anti‐inflammatory effects through astroglia in other inflammatory cells, IL‐10 has direct neuronal effects with important implications for development and neuroprotection.

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Journal of Neurochemistry

Tập 110 Số 5

1617-1627

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