Regulation of interleukin-6 expression in osteoblasts by oxidized phospholipids

Wendy Tseng; Jinxiu Lu; Gail A Bishop; Andrew D Watson; Andrew P Sage; Linda Demer; Yin Tintut

doi:10.1194/jlr.M001099

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Regulation of interleukin-6 expression in osteoblasts by oxidized phospholipids

Journal article

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Regulation of interleukin-6 expression in osteoblasts by oxidized phospholipids

Wendy Tseng, Jinxiu Lu, Gail A Bishop, Andrew D Watson, Andrew P Sage, Linda Demer and Yin Tintut

Journal of lipid research, Vol.51(5), pp.1010-1016

05/2010

DOI: 10.1194/jlr.M001099

PMCID: PMC2853427

PMID: 19965598

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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-α. 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.

calvaria

lipids

cytokines

osteoporosis

inflammation

Details

Title: Subtitle: Regulation of interleukin-6 expression in osteoblasts by oxidized phospholipids
Creators: Wendy Tseng - Department of Microbiology, University of Iowa, and the Iowa City Veterans Affairs Medical Center, Iowa City, IA
Jinxiu Lu - Department of Microbiology, University of Iowa, and the Iowa City Veterans Affairs Medical Center, Iowa City, IA
Gail A Bishop - Department of Microbiology, University of Iowa, and the Iowa City Veterans Affairs Medical Center, Iowa City, IA
Andrew D Watson - Department of Microbiology, University of Iowa, and the Iowa City Veterans Affairs Medical Center, Iowa City, IA
Andrew P Sage - Department of Microbiology, University of Iowa, and the Iowa City Veterans Affairs Medical Center, Iowa City, IA
Linda Demer - Department of Microbiology, University of Iowa, and the Iowa City Veterans Affairs Medical Center, Iowa City, IA
Yin Tintut - Department of Microbiology, University of Iowa, and the Iowa City Veterans Affairs Medical Center, Iowa City, IA
Resource Type: Journal article
Publication Details: Journal of lipid research, Vol.51(5), pp.1010-1016
DOI: 10.1194/jlr.M001099
PMID: 19965598
PMCID: PMC2853427
NLM abbreviation: J Lipid Res
ISSN: 0022-2275
eISSN: 1539-7262
Publisher: The American Society for Biochemistry and Molecular Biology
Language: English
Date published: 05/2010
Academic Unit: Microbiology and Immunology; President
Record Identifier: 9984001207702771

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