Proliferation-independent induction of macrophage cyclin D2, and repression of cyclin D1, by lipopolysaccharide.
D-type cyclins are induced in response to mitogens and are essential and rate-limiting for G1 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 cyclin D3. Previously we showed that the macrophage-activating agent lipopolysaccharide (LPS) blocks CSF-1-induced proliferation and cyclin D1 expression in macrophages. Here we report upon the effect of LPS on expression of cyclin D2 in normal mouse bone marrow-derived macrophages (BMM). Unexpectedly we found that this anti-mitogen raised levels of CSF-1-stimulated cyclin D2 mRNA and protein. Furthermore, LPS alone induced cyclin D2 but not cyclin D1. Inhibition of the MEK/ERK (MAPK/ERK kinase/extracellular signal-regulated kinase) mitogen-activated protein kinase pathway repressed LPS-induced cyclin D2 mRNA, whereas inhibition of the p38 mitogen-activated protein kinase enhanced expression. However, in contrast to cyclin D1, cyclin D2 in bone marrow-derived macrophages 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.
Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Melbourne, Australia 3050. vadivep@svhm.org.au
P K
PK
Vadiveloo
G
G
Vairo
A K
AK
Royston
U
U
Novak
J A
JA
Hamilton
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000494:pharmacology; D019938:Cyclin D1 / Q000096:biosynthesis*; D056742:Cyclin D2; D016213:Cyclins / Q000096:biosynthesis*; D004357:Drug Synergism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D015398:Signal Transduction
C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D016213:Cyclins; D008070:Lipopolysaccharides; D019938:Cyclin D1; D016173:Macrophage Colony-Stimulating Factor; D000242:Cyclic AMP; D017871:Calcium-Calmodulin-Dependent Protein Kinases