Chemokines and their receptors in the central nervous system

Chemokines are a family of proteins associated with the trafficking of leuk ocytes in physiological immune surveillance and inflammatory cell recruitme nt in host defence. They are classified into four classes based on the posi tions of key cystiene residues: C, CC, CXC, and CX3C. Chemokines act throug h both specific and shared receptors that all belong to the superfamily of G-protein-coupled receptors. Besides their well-established role in the imm une system, several recent reports have demonstrated that these proteins ls o play a role in the central nervous system (CNS). In the CNS, chemokines a re constitutively expressed by microglial cells, astrocytes, and neurons, a nd their expression can be increased after induction with inflammatory medi ators. Constitutive expression of chemokines and chemokine receptors has be en observed in both developing and adult brains, and the role played by the se proteins in the normal brain is the object of intense study by many rese arch groups. Chemokines are involved in brain development and in the mainte nance of normal brain homeostasis; these proteins play a role in the migrat ion, differentiation, and proliferation of glial and neuronal cells. The ch emokine stromal cell-derived factor 1 and its receptor, CXCR4, are essentia l for life during development, and this ligand-receptor pair has been shown to have a fundamental role in neuron migration during cerebellar formation . Chemokine and chemokine receptor expression can be increased by inflammat ory mediators, and this has in turn been associated with several acute and chronic inflammatory conditions. In the CNS, chemokines play an essential r ole in neuroinflammation as mediators of leukocyte infiltration. Their over expression has been implicated in different neurological disorders, such as multiple sclerosis, trauma, stroke, Alzheimer's disease, tumor progression , and acquired immunodeficiency syndrome-associated dementia. An emerging a rea of interest for chemokine action is represented by the communication be tween the neuroendocrine and the immune system. Chemokines have hormone-lik e actions, specifically regulating the key host physiopathological response s of fever and appetite. It is now evident that chemokines and their recept ors represent a plurifunctional family of proteins whose actions on the CNS are not restricted to neuroinflammation. These molecules constitute crucia l regulators of cellular communication in physiological and developmental p rocesses.