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Type I interferons mediate the lipopolysaccharide induction of macrophage cyclin D2
P K Vadiveloo1, H Christopoulos, U Novak
1The Bernard O'Brien Institute of Microsurgery, Fitzroy, Australia. vadivep@svhm.org.au
Abstract:
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.
Insights
Lipopolysaccharide (LPS) activates macrophages to produce cyclin D2, a process dependent on type I interferons (IFN). This study reveals type I interferons are essential mediators of LPS-induced cyclin D2 expression in macrophages.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Lipopolysaccharide (LPS) is a potent macrophage activator and antimitogen.
- Previous research indicated LPS unexpectedly induces cyclin D2 in macrophages.
- LPS stimulates macrophages to produce autocrine cytokines, suggesting a potential mediator role.
Purpose of the Study:
- To investigate if type I interferons (IFN) mediate LPS-induced cyclin D2 expression in macrophages.
- To elucidate the role of type I IFN signaling in LPS-stimulated macrophage responses.
Main Methods:
- Utilized bone marrow-derived macrophages (BMM) lacking the type I interferon receptor component (IFNAR-1).
- Stimulated BMM with LPS and assessed cyclin D2 mRNA and protein levels.
- Employed anti-IFN-alpha/beta neutralizing antibodies in normal BMM stimulated with LPS.
- Administered IFN-alpha alone to normal BMM to assess its effect on cyclin D2.
Main Results:
- BMM lacking IFNAR-1 failed to express cyclin D2 mRNA or protein upon LPS stimulation.
- Neutralizing antibodies against IFN-alpha/beta significantly reduced LPS-induced cyclin D2 levels in normal BMM.
- IFN-alpha alone was sufficient to induce cyclin D2 mRNA and protein expression in normal BMM.
Conclusions:
- Type I interferons are essential mediators of LPS-induced cyclin D2 expression in macrophages.
- This study identifies a novel role for type I IFN in regulating macrophage cell cycle progression following LPS exposure.