CXCL12-γ expression is inhibited in neuroinflammation

Abstract

CXCL12 plays a protective role in CNS autoimmunity. Expression of CXCL12-gamma, which has distinct structural and functional properties than the other isoforms of CXCL12, was determined in spinal cords of rats immunized to develop experimental autoimmune encephalomyelitis (EAE). CNS expression of CXCL12-gamma was markedly lower in EAE-prone Dark Agouti rats than in EAE-resistant Albino Oxford rats, both in spinal cord homogenates and micro-blood vessels isolated from spinal cords. Inhibition of nitric oxide (NO) synthesis in DA rats upregulated, while donation of NO in AO rats downregulated CNS expression of CXCL12-gamma. NO inhibited CXCL12-gamma expression in astrocytes in vitro. A splice variant of CXCL12-gamma which migrates into nucleolus was not detected in spinal cord or astrocytes. Thus, CXCL12-gamma is expressed in the CNS after EAE induction, but its expression is markedly suppressed in spinal cord affected with full blown inflammation. NO is an important regulator of CXCL12-gamma expression in neuroinflammation. (C) 2013 Elsevier B.V. All rights reserved.