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Inflammation

, Volume 39, Issue 1, pp 199–208 | Cite as

Silencing Triggering Receptors Expressed on Myeloid Cells-1 Impaired the Inflammatory Response to Oxidized Low-Density Lipoprotein in Macrophages

  • Houxuan Li
  • Feifei Hong
  • Shengbo Pan
  • Lang LeiEmail author
  • Fuhua YanEmail author
Article

Abstract

Atherosclerosis is a chronic progressive inflammatory disease characterized by the accumulation of lipid contents in arterial walls. Previous studies suggest participation of Toll-like receptors (TLRs) in lipid deposition and inflammatory response in vascular wall. The triggering receptor expressed on myeloid cells 1 (TREM-1) is a cell surface receptor of the immunoglobulin superfamily, which amplifies signal transduction of TLR pathway and enhances immune response to microbial infections. The aim of the present study was to investigate the effect of the oxidized low-density lipoprotein (oxLDL) on the expression of the TREM-1, as well as its engagement in proinflammatory cytokine production and foam cell formation in RAW264.7 mice macrophages. oxLDL enhanced TREM-1 and TLR-4, but not TLR-2 gene expression in macrophages; furthermore, silencing TREM-1 expression by short hairpin interfering RNA inhibited lipid phagocytosis and proinflammatory tumor necrosis factor-α (TNF-α) as well as interleukin-6 (IL-6) production in macrophages; moreover, application of synthetic antagonist, LP-17 polypeptide, reduced IL-6 production upon oxLDL stimulation in vitro and in vivo. In conclusion, in macrophages, oxLDL enhanced expression of TREM-1, which amplifies the innate immune response of TLR pathway; activation of TREM-1 contributes to atherogenesis process by enhancing proinflammatory cytokine production and foam cell formation.

KEY WORDS

triggering receptors expressed on myeloid cells-1 oxidized low-density lipoprotein Toll-like receptors macrophages, atherosclerosis 

Abbreviations

TREM-1

Triggering receptor expressed on myeloid cells 1

qPCR

Quantitative real-time polymerase chain reaction

TLR

Toll-like receptor

IL

Interleukin

TNF

Tumor necrosis factor

PRRs

Pattern recognition receptors

PAMPs

Pathogen-associated molecular patterns

oxLDL

Oxidized low-density lipoprotein

shRNA

Short hairpin interfering RNA

Notes

Acknowledgments

We thank Dr. Zhiqiang Zhang from College of Pharmacology, Fujian Medical University, for the excellent technical support in the experiment. This study was supported by the National Natural Science Foundation of China (Grant Nos. 81400516, 8100760, 81170973, and 30973326).

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Nanjing Stomatological HospitalMedical School of Nanjing UniversityNanjingChina
  2. 2.Department of PeriodontologyXiamen Stomatological HospitalXiamenChina

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