IFNγ regulates PDGF-receptor alpha expression in macrophages, THP-1 cells, and arterial smooth muscle cells

The recruitment of monocyte-derived macrophages (MDMs) and arterial smooth muscle cells (ASMCs) contributes to inflammation and development of intimal hyperplasia during atherosclerosis. Platelet-derived growth factor (PDGF) is a potent mitogen for SMC, signalling through PDGF-receptor subunits α (Rα) and β (Rβ). We have previously found that interferon gamma (IFNγ) upregulates PDGF-Rα mRNA expression in human MDM (hMDM) which causes an increased migration towards PDGF. In the present study, we found that IFNγ mediated an upregulation of PDGF-Rα mRNA also in THP-1 cells. The induction of PDGF-Rα in both hMDM and THP-1 cells was caused by STAT1 binding to the PDGF-Rα promoter. In human ASMCs, IFNγ again stimulated a transient STAT1-binding to the PDGF-Rα promoter. However, this was not followed by an upregulation of PDGF-Rα mRNA. IFNγ-stimulation resulted in augmented expression of PDGF-Rα protein in differentiated hMDM. Early hMDM only expressed an immature and not fully glycosylated form of the PDGF-Rα protein. In contrast, THP-1 cells did not synthesize PDGF-Rα protein, implying further posttranscriptional inhibition. Our results contribute to a better understanding of the complex regulation of PDGF-Rα expression and how proinflammatory factors may contribute to PDGF-related hyperplasia in vascular diseases.