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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Neurotensin receptor-3/sortilin mediates neurotensin- induced cytokine/chemokine expression in a murine microglial cell line.

We show that the type I neurotensin receptor-3 (also called sortilin) is the only known neurotensin receptor expressed in a murine microglial cell line and that its activation leads to phosphorylation of both extracellular signaling-regulated (Erk1/2) and Akt kinases. Using semiquantitative reverse-transcriptase (RT) PCR, we demonstrate that neurotensin induces gene expression of several cytokines/chemokines including macrophage inflammatory protein (MIP)-2, monocyte chemotactic protein (MCP)-1, interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. This induction is dependent on both phosphatidylinositol 3-kinase and mitogen-activated protein kinases pathways. We observe that the effect of neurotensin on cytokine/chemokine expression is inhibited by the neurotensin receptor-3 propeptide, a selective ligand of this receptor. These results demonstrate that the neurotensin receptor-3 is functional in microglial cells where it mediates the induction of chemokines/cytokines expression by neurotensin.[1]


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