| First Author | Campbell IL | Year | 2005 |
| Journal | Brain Res Brain Res Rev | Volume | 48 |
| Issue | 2 | Pages | 166-77 |
| PubMed ID | 15850655 | Mgi Jnum | J:98646 |
| Mgi Id | MGI:3579586 | Doi | 10.1016/j.brainresrev.2004.12.006 |
| Citation | Campbell IL (2005) Cytokine-mediated inflammation, tumorigenesis, and disease-associated JAK/STAT/SOCS signaling circuits in the CNS. Brain Res Brain Res Rev 48(2):166-77 |
| abstractText | Cytokines are plurifunctional mediators of cellular communication. The CNS biology of this family of molecules has been explored by transgenic approaches that targeted the expression of individual cytokine genes to specific cells in the CNS of mice. Such transgenic animals exhibit wide-ranging structural and functional alterations that are linked to the development of distinct neuroinflammatory responses and gene expression profiles specific for each cytokine. The unique actions of individual cytokines result from the activation of specific receptor-coupled cellular signal transduction pathways such as the JAK/STAT tyrosine kinase signaling cascade. The cerebral expression of various STATs, their activation, as well as that of the major physiological inhibitors of this pathway, SOCS1 and SOCS3, is highly regulated in a stimulus- and cell-specific fashion. The role of the key IFN signaling molecules STAT1 or STAT2 was studied in transgenic mice (termed GIFN) with astrocyte-production of IFN-alpha that were null or haploinsufficient for these STAT genes. Surprisingly, these animals developed either more severe and accelerated neurodegeneration with calcification and inflammation (GIFN/STAT1 deficient) or severe immunoinflammation and medulloblastoma (GIFN/STAT2 deficient). STAT dysregulation may result in a signal switch phenomenon in which one cytokine acquires the apparent function of an entirely different cytokine. Therefore, for cytokines such as the IFNs, the receptor-coupled signaling process is complex, involving the coexistence of multiple JAK/STAT as well as alternative pathways. The cellular compartmentalization and balance in the activity of these pathways ultimately determines the repertoire and nature of CNS cytokine actions. |
