Pk. Vadiveloo et al., PROLIFERATION-INDEPENDENT INDUCTION OF MACROPHAGE CYCLIN D2, AND REPRESSION OF CYCLIN D1, BY LIPOPOLYSACCHARIDE, The Journal of biological chemistry, 273(36), 1998, pp. 23104-23109
D-type cyclins are induced in response to mitogens and are essential,
and rate-limiting for G(1) phase progression in normal mammalian cells
. Macrophages proliferating in response to colony-stimulating factor-1
(CSF-1) express cyclin D1 and to a lesser extent cyclin D2 but not cy
clin D3, Previously we showed that the macrophage-activating agent lip
opolysaccharide (LPS) blocks CSF-1-induced proliferation and cyclin D1
expression in macrophages, Here we report upon the effect of LPS on e
xpression of cyclin D2 in normal mouse bone marrow-derived macrophages
(BMM). Unexpectedly me found that this anti-mitogen raised levels of
CSF-1-stimulated cyclin D2 mRNA and protein. Furthermore, LPS alone in
duced cyclin Ha but not cyclin D1. Inhibition of the MEK/ERK (MAPK/ERK
kinase/extracellular signal-regulated kinase) mitogen-activated prote
in kinase pathway repressed LPS-induced cyclin D2 mRNA, whereas inhibi
tion of the p38 mitogen-activated protein kinase enhanced expression.
However, in contrast to cyclin D1, cyclin D2 in bone marrow-derived ma
crophages did not appear to be regulated by protein kinase A pathways.
The present data (a) show elevation of a D-type cyclin in the absence
of proliferation, (b) demonstrate inverse regulation of two distinct
D-type cyclins under identical conditions, and (c) suggest that cyclin
D2 plays a role in macrophage activation by LPS.