| First Author | Li H | Year | 2013 |
| Journal | Neuroscience | Volume | 253 |
| Pages | 89-99 | PubMed ID | 24012746 |
| Mgi Jnum | J:207434 | Mgi Id | MGI:5556365 |
| Doi | 10.1016/j.neuroscience.2013.08.051 | Citation | Li H, et al. (2013) PI3Kgamma inhibition alleviates symptoms and increases axon number in experimental autoimmune encephalomyelitis mice. Neuroscience 253:89-99 |
| abstractText | Phosphoinositide 3-kinase gamma (PI3Kgamma) is a shared downstream component of chemokine-mediated signaling pathways and regulates migration, proliferation and activation of inflammatory cells. PI3Kgamma has been shown to play a crucial role in regulating inflammatory responses during the progression of several diseases. We investigated the potential function of PI3Kgamma in mediating inflammatory reactions and the development of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). We found that systemic treatment with selective PI3Kgamma inhibitor AS-604850 significantly reduced the number of infiltrated leukocytes in the CNS and ameliorated the clinical symptoms of EAE mice. Treatment with this PI3Kgamma inhibitor enhanced myelination and axon number in the spinal cord of EAE mice. Consistently, we demonstrated that PI3Kgamma deletion in knockout mice mitigates the clinical sign of EAE compared to PI3Kgamma+/+ controls. PI3Kgamma deletion increased the number of axons in the lumbar spinal cord, including descending 5-HT-positive serotonergic fiber tracts. Our results indicate that PI3Kgamma contributes to development of autoimmune CNS inflammation and that PI3Kgamma blockade may provide a great potential for treating patients with MS. |
