The growth-related gene product beta induces sphingomyelin hydrolysis and activation of c-Jun N-terminal kinase in rat cerebellar granule neurones

The growth-related gene product beta (GRO beta) is a small chemoattractant cytokine that belongs to the CXC chemokine family, and GRO beta receptors are expressed in the brain, including the cerebellum. We demonstrate that rat cerebellar granule neurones express the GRO beta receptor CXCR2. We also show that, in addition to the known stimulation of a phosphoinositide-specific phospholipase C, GRO beta activates both neutral (N-) and acidic (A-) sphingomyelinases (SMase) and the stress-activated c-Jun N-terminal kinase I (JNK1). Although both exogenous ceramide and bacterial SMase stimulate JNH1, GRO beta-induced JNK1 activation is an event probably in dependent of ceramide generated by A-SMase, since it is maintained in the presence of compounds that block A-SMase activity. This is the first report on the activation of the SMase pathway by chemokines.