Chemokines and their receptors are physiologically expressed in the central nervous system (CNS) both in neuronal and glial cells, where they play specific roles in neurogenesis, neuromodulation, neuron-glia communication, and neuroprotection (1). CXCL16 is a transmembrane chemokine that only recently has been found to be expressed on glial and endothelial cells in the CNS (2), and that, upon cleavage by metalloproteases, can be released in a soluble form that is physiologically present in the cerebral spinal fluid (CSF). Moreover, during brain inflammatory diseases, the level of soluble CXCL16 in the CSF is increased (3). Glutamate (Glu) excitotoxicity represents mechanism that is ultimately responsible of neuronal cell death in several inflammatory and neurodegenerative disorders such as ischemia, ALS, Alzheimer, Parkinson and Huntington's diseases. We investigated the role of CXCL16 in protecting neurons from cell death upon Glu excitotoxic insult and found that, when CXCL16 was administrated during Glu challenge, neuronal cell death was reduced. This effects was totally prevented in CXCR6-/- mice. Moreover, we found that astrocytes were major players in mediating CXCL16 neuroprotection, and that adenosine, acting through its own receptor type 3, A3R, was necessary to allow chemokine neuroprotection.

(1) de Haas et al. 2007. Mol. Neurobiol. 36, 137–151.

(2) Ludwig et al. 2005. J. Neurochem. 93, 1293–1303.

(3) le Blanc et al. 2006. Neurosci. Lett. 397, 145–148.