Differentiated human NT2-N neurons were shown to express CCR5 and CXCR4 chemokine receptor mRNA and protein, and to be responsive to the chemokines CCL5 and CXCL12. Using cDNA microarray technology, CCL5 was found to induce a distinct transcriptional program, with reproducible induction of 46 and 9 genes after 2 and 8 hr of treatment, respectively. Conversely, downregulation of 20 and 7 genes was observed after 2 and 8 hr of treatment, respectively. Modulation of a selected panel of CCL5-responsive genes was also confirmed by quantitative RT-PCR and Western blot and compared to gene expression changes induced by CXCL12 treatment. Gene clustering identified distinct functional subsets of CCL5-responsive molecules, and a significant number of expressed sequence tags encoding unknown genes. CCL5-responsive genes comprise a significant number of enzymes, transcription factors, and miscellaneous molecules involved in neuronal survival and differentiation, including neurite outgrowth and synaptogenesis. Our results suggest that CCL5 biological functions might go beyond its recognized chemotactic activity in the central nervous system, in particular with regard to the control of neural plasticity events both during development and in postnatal life.
Copyright 2004 Wiley-Liss, Inc.