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.
Vadiveloo
P K
PK
The Bernard O'Brien Institute of Microsurgery, Fitzroy, Australia. vadivep@svhm.org.au
Christopoulos
H
H
Novak
U
U
Kola
I
I
Hertzog
P J
PJ
Hamilton
J A
JA
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D056742:Cyclin D2; D016213:Cyclins / Q000096:biosynthesis*; D007370:Interferon Type I / Q000502:physiology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout
C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D016213:Cyclins; D007370:Interferon Type I; D008070:Lipopolysaccharides