The Journal of Immunology, Vol 153, Issue 1 378-383, Copyright © 1994 by American Association of Immunologists

ARTICLES

IL-1 down-regulates platelet-derived growth factor-alpha receptor gene expression at the transcriptional level in human osteoblastic cells

JF Xie, J Stroumza and DT Graves
Department of Oral Biology, Boston University School of Graduate Dentistry, MA.

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.

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