IFN gamma regulates PDGF-receptor alpha expression in macrophages, THP-1 cells, and arterial smooth muscle cells
2006 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 184, no 1, 39-47 p.Article in journal (Refereed) Published
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 alpha (Ralpha) and beta (Rbeta). We have previously found that interferon gamma (IFNgamma) upregulates PDGF-Ralpha mRNA expression in human MDM (hMDM) which causes an increased migration towards PDGF. In the present study, we found that IFNgamma mediated an upregulation of PDGF-Ralpha mRNA also in THP-1 cells. The induction of PDGF-Ralpha in both hMDM and THP-1 cells was caused by STAT1 binding to the PDGF-Ralpha promoter. In human ASMCs, IFNgamma again stimulated a transient STAT1-binding to the PDGF-Ralpha promoter. However, this was not followed by an upregulation of PDGF-Ralpha mRNA. IFNgamma-stimulation resulted in augmented expression of PDGF-Ralpha protein in differentiated hMDM. Early hMDM only expressed an immature and not fully glycosylated form of the PDGF-Ralpha protein. In contrast, THP-1 cells did not synthesize PDGF-Ralpha protein, implying further posttranscriptional inhibition. Our results contribute to a better understanding of the complex regulation of PDGF-Ralpha expression and how proinflammatory factors may contribute to PDGF-related hyperplasia in vascular diseases.
Place, publisher, year, edition, pages
Elsevier, 2006. Vol. 184, no 1, 39-47 p.
PDGF, Receptor, IFNγ, Atherosclerosis, Transcriptional regulation, STAT
Other Basic Medicine
Research subject Medical sciences
IdentifiersURN: urn:nbn:se:his:diva-11384DOI: 10.1016/j.atherosclerosis.2005.03.026ISI: 000234730100006PubMedID: 15871904ScopusID: 2-s2.0-28344447320OAI: oai:DiVA.org:his-11384DiVA: diva2:847234