CXCL16 orchestrates adenosine A 3 receptor and MCP-1/CCL2 activity to protect neurons from excitotoxic cell death in the CNS

Maria Rosito, Cristina Deflorio, Cristina Limatola, Flavia Trettel

Research output: Contribution to journalArticle

Abstract

A role for chemokines as molecules mediating neuron-glia cross talk has emerged in recent years, both in physiological and pathological conditions.Wedemonstrate here for the first time that the chemokine CXCL16 and its unique receptor CXCR6 are functionally expressed in the CNS, and induce neuroprotection against excitotoxic damage due to excessive glutamate (Glu) exposure and oxygen glucose deprivation (OGD). In mice and rats we found that, to exert neuroprotection, CXCL16 requires the presence of extracellular adenosine (ADO), and that pharmacological or genetic inactivation of the ADO A 3 receptor, A 3R, prevents CXCL16 effect. In experiments with astrocytes cocultured with cxcr6 gfp/gfp hippocampal cells, we demonstrate that CXCL16 acts directly on astrocytes to release soluble factors that are essential to mediate neuroprotection. In particular, we report that (1) upon stimulation with CXCL16 astrocytes release monocyte chemoattractant protein-1/CCL2 and (2) the neuroprotective effect of CXCL16 is reduced in the presence of neutralizing CCL2 antibody. In conclusion, we found that chemokine CXCL16 is able to mediate cross talk between astrocytes and neighboring neurons and, in pathological conditions such as excessive Glu or OGD exposure, is able to counteract neuronal cell death through an ADO-dependent chemokine-induced chemokine-release mechanism.

Original languageEnglish
Pages (from-to)3154-3163
Number of pages10
JournalJournal of Neuroscience
Volume32
Issue number9
DOIs
Publication statusPublished - Feb 29 2012

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'CXCL16 orchestrates adenosine A 3 receptor and MCP-1/CCL2 activity to protect neurons from excitotoxic cell death in the CNS'. Together they form a unique fingerprint.

  • Cite this