TGFbeta1 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 likely a crucial point for the regulation of chemokine action. Here we show that CC chemokine receptor 1 (CCR1) expression by primary mouse astrocytes is increased after transforming growth factor beta1 (TGFbeta1) stimulation. TGFbeta1 caused a pronounced up-regulation of CCR1 mRNA in a concentration- and time-dependent manner. TGFbeta1-mediated increase of CCR1 mRNA accumulation resulted in increased CCR1 protein expression and augmented cell migration to a physiological ligand, macrophage inflammatory protein-1alpha (MIP-1alpha). The half life of CCR1 mRNA in the presence and absence of TGFbeta1 stimulation was comparable, suggesting that TGFbeta1-induced CCR1 mRNA accumulation occurred at the transcriptional level. TGFbeta1 did not affect CCR1 mRNA expression in hematopoietic cells, indicating that TGFbeta1 effect on CCR1 expression in primary astrocytes is cell-type specific. This is the first evidence that TGFbeta1 may modulate central nervous system (CNS) inflammation in part by affecting chemokine receptor expression on astrocytes.
Han
Y
Y
Department of Neurosciences, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Wang
J
J
Zhou
Z
Z
Ransohoff
R M
RM
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002633:Chemotaxis / Q000187:drug effects; D005260:Female; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000378:metabolism; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D015854:Up-Regulation
C515301:Ccr1 protein, mouse; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D054389:Receptors, CCR1; D019707:Receptors, Chemokine; D016212:Transforming Growth Factor beta