Differential Expression of Colony-Stimulating Factor (CSF) in Murine Macrophage Clones : Interferon-γ-Mediated Inhibition of CSF Production

Abstract

Bioassay and northern blot analyses revealed that, among several functional murine macro-phage (Mφ) clones, lipopolysaccharide (LPS) stimulation generated in distinct induction levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and macrophage colony-stimulating factor (M-CSF). When compared with these induction profiles, the Mφ clones could be classified into two types ; G type (G-CSF⁺⁺⁺GM-CSF^-M-CSF⁺) and GM type (G-CSF±GM-CSF⁺⁺⁺M-CSF⁺) of Mφ clones. Unlike G-CSF and GM-CSF that were inducible factors, M-CSF mRNA was constitutively expressed without stimulation and was differentially controlled between the G and GM types ; LPS induction decreased M-CSF mRNA in the former, but increased it in the latter. Further northern blot analysis revealed that interferon-γ (IFN-γ) suppressed constitutive expression of M-CSF mRNA, and that costimulation with both LPS and IFN-γ reduced expression of G-CSF and M-CSF mRNA in the G type of Mφ clone, but induced higher expression of GM-CSF and M-CSF mRNAs in the GM type of Mφ clone compared with LPS alone. However, in either case, IFN-γ completely inhibited LPS-induced production of active CSF of the Mφ clones, which was observed even in IFN-γ pretreatment, and also abrogated autoactivation of GM-CSF. Our present results suggested that murine Mφ clones had differentially regulated expressions of CSFs and that IFN-γ had a regulatory function of inhibiting CSF production of murine Mφs.