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.
Dicou
Eleni
E
Institut de Pharmacologie Moléculaire et Cellulaire, du CNRS, Valbonne, France. dicou@ipmc.cnrs.fr
Vincent
Jean-Pierre
JP
Mazella
Jean
J
D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D002460:Cell Line; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D017628:Microglia / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009496:Neurotensin / Q000502:physiology*; D000099183:Sortilin
D033942:Adaptor Proteins, Vesicular Transport; D018925:Chemokines; D016207:Cytokines; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D009496:Neurotensin; D000099183:Sortilin