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

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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.

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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

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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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Authors and Affiliations

  1. Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, 210008, China

    Houxuan Li, Lang Lei & Fuhua Yan

  2. Department of Periodontology, Xiamen Stomatological Hospital, Xiamen, Fujian, 361000, China

    Feifei Hong & Shengbo Pan

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  1. Houxuan Li
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  4. Lang Lei
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Correspondence to Lang Lei or Fuhua Yan.

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Li, H., Hong, F., Pan, S. et al. Silencing Triggering Receptors Expressed on Myeloid Cells-1 Impaired the Inflammatory Response to Oxidized Low-Density Lipoprotein in Macrophages. Inflammation 39, 199–208 (2016). https://doi.org/10.1007/s10753-015-0239-5

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