TGF beta 1 selectively up-regulates CCR1 expression in primary murine astrocytes

Chemokine receptors dictate the cellular responses to chemokines on target cells. Therefore, the regulation of expression of chemokine receptors is li kely a crucial point for the regulation of chemokine action. Here we show t hat CC chemokine receptor 1 (CCR1) expression by primary mouse astrocytes i s increased after transforming growth factor beta 1 (TGF beta 1) stimulatio n. TGF beta 1 caused a pronounced up-regulation of CCR1 mRNA in a concentra tion- and time-dependent manner. TGF beta 1-mediated increase of CCR1 mRNA accumulation resulted in increased CCR1 protein expression and augmented ce ll migration to a physiological ligand, macrophage inflammatory protein-1 a lpha (MIP-1 alpha). The half life of CCR1 mRNA in the presence and absence of TGF beta 1 stimulation was comparable, suggesting that TGF beta 1-induce d CCR1 mRNA accumulation occurred at the transcriptional level. TGF beta 1 did not affect CCR1 mRNA expression in hematopoietic cells, indicating that TGF beta 1 effect on CCR1 expression in primary astrocytes is cell-type sp ecific. This is the first evidence that TGF beta 1 may modulate central ner vous system (CNS) inflammation in part by affecting chemokine receptor expr ession on astrocytes. GLIA 30:1-10, 2000. (C) 2000 Wiley-Liss, Inc.