Type I Interferons Mediate the Lipopolysaccharide Induction of Macrophage Cyclin D2

Lipopolysaccharide (LPS) is a powerful macrophage-activating agent and antimitogen. We recently showed that LPS unexpectedly induces cyclin D2 in macrophages. Since LPS stimulates macrophages to produce autocrine-acting cytokines, we examined whether LPS induction of cyclin D2 was mediated by one such type of cytokine, type I interferons (IFN). We report that bone marrow-derived macrophages (BMM) lacking a component of the type I interferon receptor (IFNAR-1) do not express cyclin D2 mRNA or protein in response to LPS stimulation (0.01-1 microg/ml for 7-30 h). Consistent with this result, addition of anti-IFN-alpha/beta neutralizing antibodies reduced levels of LPS-stimulated cyclin D2 in normal BMM. Furthermore, IFN-alpha alone induced cyclin D2 mRNA and protein in normal BMM. Thus, we have identified a new role for type I IFN in macrophages, namely, as essential mediators of LPS-stimulated cyclin D2 expression.