Interferon-γ suppresses PDGF production from THP-1 cells and blood monocyte-derived macrophages

Chiya Kosaka, Junichi Masuda, Kentaro Shimokado, Katsuhiro Zen, Tasuku Yokota, Toshiyuki Sasaguri, Jun Ogata

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

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-γ (IFN-γ), 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-γ (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-γ treatment. Radioimmunoassays for PDGF also revealed a decrease in both PDGFAA and -BB in the conditioned medium with IFN-γ 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-γ 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-γ 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-γ 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-γ.

Original languageEnglish
Pages (from-to)75-87
Number of pages13
JournalAtherosclerosis
Volume97
Issue number1
DOIs
Publication statusPublished - Nov 1992
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Interferon-γ suppresses PDGF production from THP-1 cells and blood monocyte-derived macrophages'. Together they form a unique fingerprint.

Cite this