Document Detail


Interferon-gamma suppresses PDGF production from THP-1 cells and blood monocyte-derived macrophages.
MedLine Citation:
PMID:  1445496     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Involvement of the immunological mechanisms in atherogenesis has recently been suggested by immunohistological detection of macrophages and T lymphocytes in atherosclerotic lesions. In the present study, we have investigated the regulatory effect of interferon-gamma (IFN-gamma), a cytokine secreted by activated T cells, on the production and secretion of platelet-derived growth factor (PDGF) from macrophages in culture. The human monocytic leukemia cell line, THP-1, was treated with phorbol 12-myristate 13-acetate (PMA) for 24 h to induce macrophage differentiation and PDGF production, and then various doses of recombinant human IFN-gamma (0-1000 I.U./ml) were added to the culture. After 48 h, the conditioned medium and the cells were harvested and analyzed for PDGF production. PDGF-dependent mitogenic activity in the conditioned medium, estimated by neutralization of mitogenic activity with anti-PDGF antibody, was suppressed by IFN-gamma treatment. Radioimmunoassays for PDGF also revealed a decrease in both PDGF-AA and -BB in the conditioned medium with IFN-gamma treatment, whereas neither total cell DNA as an indication of cell number nor overall protein synthesis based on [3H]leucine incorporation were decreased. Northern analysis of total RNA extracted from the cells demonstrated that IFN-gamma suppressed the level of PDGF mRNA. Analysis of mRNA degradation in the presence of actinomycin D demonstrated that the decrease in PDGF mRNA was not due to enhanced degradation of mRNA. A similar inhibitory effect of IFN-gamma on PDGF mRNA levels was also found in monocyte-derived macrophages cultured in the presence of granulocyte-macrophage colony stimulating factor. These results suggest that IFN-gamma modulates production and secretion of PDGF from macrophages and that the functions of macrophages in atherogenesis may be regulated by the cellular interactions between T cells and macrophages through the action of cytokines such as IFN-gamma.
Authors:
C Kosaka; J Masuda; K Shimokado; K Zen; T Yokota; T Sasaguri; J Ogata
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Atherosclerosis     Volume:  97     ISSN:  0021-9150     ISO Abbreviation:  Atherosclerosis     Publication Date:  1992 Nov 
Date Detail:
Created Date:  1992-12-14     Completed Date:  1992-12-14     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  75-87     Citation Subset:  IM    
Affiliation:
National Cardiovascular Center Research Institute, Osaka, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Division
Cells, Cultured
Culture Media, Conditioned
DNA / biosynthesis
Fibroblasts / cytology,  metabolism
Gene Expression
Humans
Interferon-gamma / pharmacology*
Leukemia, Monocytic, Acute / metabolism*
Macrophages / metabolism*
Mice
Platelet-Derived Growth Factor / biosynthesis*,  genetics
RNA, Messenger / analysis
Radioimmunoassay
Tetradecanoylphorbol Acetate / pharmacology
Tumor Cells, Cultured / metabolism
Chemical
Reg. No./Substance:
0/Culture Media, Conditioned; 0/Platelet-Derived Growth Factor; 0/RNA, Messenger; 16561-29-8/Tetradecanoylphorbol Acetate; 82115-62-6/Interferon-gamma; 9007-49-2/DNA

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