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IFNgamma regulates ...
Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Andra medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Other Basic Medicine (hsv//eng)
Nyckelord
- Animals
- Arteries
- cytology
- metabolism
- Blotting
- Western
- Cells
- Cultured
- Female
- Humans
- Interferon Type II
- pharmacology
- Macrophages
- metabolism
- Muscle
- Smooth
- Vascular
- cytology
- metabolism
- Phosphorylation
- drug effects
- RNA
- Messenger
- genetics
- Receptor
- Platelet-Derived Growth Factor alpha
- genetics
- metabolism
- Reverse Transcriptase Polymerase Chain Reaction
- STAT1 Transcription Factor
- drug effects
- metabolism
- Swine
- Up-Regulation
- drug effects
- PDGF
- Medical sciences
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Morelli, Paula I
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Martinsson, Sofi ...
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Östergren Lundén ...
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Fridén, Vincent, ...
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Moses, Jonatan, ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Andra medicinska ...
- Artiklar i publikationen
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Atherosclerosis
- Av lärosätet
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Göteborgs universitet
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Högskolan i Skövde