Macrophage proliferation in atherosclerosis.
Oxidized LDL can induce an increase in intracellular calcium concentration and the activation of protein kinase C in mouse peritoneal macrophages. The activation of protein kinase C leads to the release into the culture medium of granulocyte-macrophage colony-stimulating factor, which plays a priming role in oxidized LDL-induced macrophage proliferation. The expression of granulocyte-macrophage colony-stimulating factor in macrophages by oxidized LDL is positively regulated in the 5'-flanking region of granulocyte-macrophage colony-stimulating factor gene from sequence -169 to -160, but negatively regulated from -91 to -82. Granulocyte-macrophage colony-stimulating factor released by oxidized LDL from macrophages induces proliferation in autocrine or paracrine fashion via the activation of phosphatidylinositol 3-kinase. The capacity of oxidized LDL to induce macrophage proliferation in vitro may be involved in the enhanced progression of atherosclerosis in vivo.
Sakai
M
M
Department of Metabolic Medicine, Kumamoto University School of Medicine, Japan.
Kobori
S
S
Miyazaki
A
A
Horiuchi
S
S
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D010741:Phospholipases A / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D051116:Receptors, Scavenger; D015398:Signal Transduction
D008077:Lipoproteins, LDL; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; C099252:oxidized low density lipoprotein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011493:Protein Kinase C; D010741:Phospholipases A; D002118:Calcium