Interleukin-10 provides direct trophic support to neurons.
Interleukin (IL)-10, a prototypical anti-inflammatory cytokine, has been shown to provide beneficial effects in neuronal injury in vivo but 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 glutamate in 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-x(L); under stress conditions IL-10 blocks cytochrome c release and caspase cleavage. IL-10 activation of the canonical nuclear factor kappaB pathway enhanced translocation of p50 and p65 and enhanced their binding to kappaB 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.
Zhou
Zhigang
Z
Department of Neurology, University of Michigan and Ann Arbor VA Healthcare System, Ann Arbor, Michigan, USA.
Peng
Xiangmin
X
Insolera
Ryan
R
Fink
David J
DJ
Mata
Marina
M
D000818:Animals; D001253:Astrocytes / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018836:Inflammation Mediators / Q000502:physiology; D016753:Interleukin-10 / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D053701:Receptors, Interleukin-10 / Q000819:agonists / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000196:embryology / Q000502:physiology
D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D053701:Receptors, Interleukin-10; D016753:Interleukin-10