Department of Oral Biology , Boston University School of Graduate Dentistry , MA .
J Immunol 153 : 378-83 ( 1994)
Abstract
Regulation of the platelet-derived growth factor ( PDGF)-alpha receptor is thought to play an important role in pathophysiologic processes .
Previously , we have reported that IL-1 has the potential to regulate PDGF-induced biologic activity in both normal human osteoblastic cells and the human osteoblastic cell line , MG-63 , by decreasing the expression of PDGF-alpha receptor mRNA .
In the present studies , we analyzed the effects of IL-1 on transcription rates and the stability of PDGF-alpha receptor mRNA in MG-63 cells .
The data indicate that the t1/2 of PDGF-alpha receptor mRNA is approximately 3.3 h after incubation with the RNA II polymerase transcription inhibitor 5,6-dichloro-1 beta-D-ribofuranosylbenzimidazole ( DRB ) .
Approximately the same t1/2 ( 3.1 h ) was obtained when osteoblastic cells were incubated with IL-1 .
The t1/2 for PDGF-alpha receptor mRNA for cells incubated with both IL-1 and DRB was 3 h . This finding suggests that the levels of PDGF-alpha receptor mRNA transcripts are not regulated by post-transcriptional mechanisms .
Results of nuclear run-on analysis were consistent with this conclusion , demonstrating that IL-1 modulates PDGF-alpha receptor gene expression at the transcriptional level .
Surprisingly , incubation of cells with cycloheximide also caused down-regulation of PDGF-alpha receptor mRNA , which suggests that synthesis of a labile factor is necessary for constitutive expression .
The functional consequence of down-regulation of PDGF-alpha receptors by IL-1 was also assessed .
By using chemotaxis assays , we demonstrated that IL-1 significantly inhibited PDGF-AA-mediated migration in human MG-63 osteoblastic sarcoma cells .