RRC ID 18734
Author Tseng W, Lu J, Bishop GA, Watson AD, Sage AP, Demer L, Tintut Y.
Title Regulation of interleukin-6 expression in osteoblasts by oxidized phospholipids.
Journal J Lipid Res
Abstract Epidemiological evidence suggests that cardiovascular disease is associated with osteoporosis, independent of age. Bone resorptive surface is increased in mice on a high-fat diet, and osteoclastic differentiation of bone marrow preosteoclasts is promoted by oxidized phospholipids. Because osteoclastic differentiation requires cytokines produced by osteoblasts, we hypothesized that the stimulatory mechanism of oxidized phospholipids is via induction of osteoclast-regulating cytokines in osteoblasts. To investigate the effects of oxidized phospholipids on expression of such cytokines, murine calvarial preosteoblasts, MC3T3-E1, were treated with oxidized 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphocholine (ox-PAPC), an active component of oxidized lipoproteins. Results showed that ox-PAPC increased expression of interleukin-6 (IL-6) and tumor necrosis factor-alpha. IL-6 expression was also elevated in calvarial tissues from hyperlipidemic but not in wild-type mice. Ox-PAPC also induced IL-6 protein levels in both MC3T3-E1 and primary calvarial cells. Promoter-reporter assay analysis showed that ox-PAPC, but not PAPC, induced murine IL-6 promoter activity. Effects of ox-PAPC on IL-6 expression and the promoter activity were attenuated by H89, a PKA inhibitor. Analysis of deletion and mutant IL-6 promoter constructs suggested that CAAT/enhancer binding protein (C/EBP) partly mediates the ox-PAPC effects. Taken together, the data suggest that oxidized phospholipids induce IL-6 expression in osteoblasts in part via C/EBP.
Volume 51(5)
Pages 1010-6
Published 2010-5-1
DOI 10.1194/jlr.M001099
PII S0022-2275(20)41056-9
PMID 19965598
PMC PMC2853427
MeSH Animals CCAAT-Enhancer-Binding Proteins / genetics Cell Line Gene Expression Regulation / drug effects* Interleukin-6 / genetics* Intracellular Space / drug effects Intracellular Space / metabolism Mice Osteoblasts / cytology Osteoblasts / drug effects* Osteoblasts / metabolism* Oxidation-Reduction Phosphatidylcholines / metabolism Phosphatidylcholines / pharmacology Phospholipids / metabolism* Phospholipids / pharmacology* RNA, Messenger / genetics RNA, Messenger / metabolism Response Elements / genetics Transcription, Genetic
IF 4.483
Times Cited 14
Human and Animal Cells MC3T3-E1(RCB1126)