Jf. Xie et al., IL-1 DOWN-REGULATES PLATELET-DERIVED GROWTH-FACTOR-ALPHA RECEPTOR GENE-EXPRESSION AT THE TRANSCRIPTIONAL LEVEL IN HUMAN OSTEOBLASTIC CELLS, The Journal of immunology, 153(1), 1994, pp. 378-383
Regulation of the platelet-derived growth factor (PDCF)-alpha receptor
is thought to play an important role in pathophysiologic processes. P
reviously, we have reported that IL-1 has the potential to regulate PD
GF-induced biologic activity in both normal human osteoblastic cells a
nd the human osteoblastic cell line, MG-63, by decreasing the expressi
on of PDGF-alpha receptor mRNA. In the present studies, we analyzed th
e effects of IL-1 on transcription rates and the stability of PDGF-alp
ha receptor mRNA in MC-63 cells. The data indicate that the t(1/2) 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-ri
bofuranosylbenzimidazole (DRB). Approximately the same t(1/2) (3.1 h)
was obtained when osteoblastic cells were incubated with IL-1. The t(1
/2) for PDGF-alpha receptor mRNA for cells incubated with both IL-1 an
d DRB was 3 h. This finding suggests that the levels of PDGF-alpha rec
eptor mRNA transcripts are not regulated by posttranscriptional mechan
isms. Results of nuclear run-on analysis were consistent with this con
clusion, demonstrating that IL-1 modulates PDGF-alpha receptor gene ex
pression at the transcriptional level. Surprisingly, incubation of cel
ls with cycloheximide also caused down-regulation of PDGF-alpha recept
or mRNA, which suggests that synthesis of a labile factor is necessary
for constitutive expression. The functional consequence of down-regul
ation of PDGF-alpha receptors by IL-1 was also assessed. By using chem
otaxis assays, we demonstrated that IL-1 significantly inhibited PDGF-
AA-mediated migration in human MG-63 osteoblastic sarcoma cells.