title: Interferon-gamma suppresses PDGF production from THP-1 cells and blood monocyte-derived macrophages.
abstract: 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.affiliation: National Cardiovascular Center Research Institute, Osaka, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Kosaka
authors.forename: J
authors.initials: J
authors.lastname: Masuda
authors.forename: K
authors.initials: K
authors.lastname: Shimokado
authors.forename: K
authors.initials: K
authors.lastname: Zen
authors.forename: T
authors.initials: T
authors.lastname: Yokota
authors.forename: T
authors.initials: T
authors.lastname: Sasaguri
authors.forename: J
authors.initials: J
authors.lastname: Ogata
mesh_terms: D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004247:DNA / Q000096:biosynthesis; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007948:Leukemia, Monocytic, Acute / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011863:Radioimmunoassay; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D007371:Interferon-gamma; D004247:DNA; D013755:Tetradecanoylphorbol Acetate