Neurotensin receptor-3/sortilin mediates neurotensin-induced cytokine/chemokine expression in a murine microglial cell line
✍ Scribed by Eleni Dicou; Jean-Pierre Vincent; Jean Mazella
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 261 KB
- Volume
- 78
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
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)‐1β and tumor necrosis factor (TNF)‐α. 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. © 2004 Wiley‐Liss, Inc.