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Electronegative LDL Induces M1 Polarization of Human Macrophages Through a LOX-1-Dependent Pathway

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Abstract

In response to environmental stimuli, monocytes undergo polarization into classically activated (M1) or alternatively activated (M2) states. M1 and M2 macrophages exert opposing pro- and anti-inflammatory properties, respectively. Electronegative low-density lipoprotein (LDL) (LDL(−)) is a naturally occurring mildly oxidized LDL found in the plasma of patients with hypercholesterolemia, diabetes, and acute myocardial infarction, and has been shown to involve in the pathogenesis of atherosclerosis. In this study, we examined the effects of LDL(−) on macrophage polarization and the involvement of lectin-like oxidized LDL receptor-1 (LOX-1) in this process. THP-1 macrophages were treated with native LDL (nLDL) or LDL(−), and then the expression of M1/M2-related surface markers and cytokines were evaluated. The results show that treatment with LDL(−) resulted in profound increase in proinflammatory cytokines, IL-1β, IL-6, and TNF-α, and M1-surface marker CD86; however, M2-related cytokines, IL-10 and TGF-β, and M2-surface marker CD206 were not changed by LDL(−). Untreated or nLDL-treated cells were used as control. LDL(−)-induced M1 polarization and secretion of proinflammatory cytokines were diminished in LOX-1 knockdown cells. Taken together, the results show that LDL(−) promotes differentiation of human monocytes to M1 macrophages through a LOX-1-dependent pathway, and explore the contribution of LDL(−) and LOX-1 to the development of chronic inflammation in atherosclerosis.

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Abbreviations

Arg-1:

Arginase-1

IL:

Interleukin

KD:

Knockdown

LDL:

Low-density lipoprotein

LDL(-):

Electronegative LDL

LOX-1:

Lectin-like oxidized LDL receptor-1

nLDL:

Native LDL

NLRP3:

NOD-, LRR-, and pyrin domain-containing protein 3

NF:

Nuclear factor

oxLDL:

Oxidized low-density lipoprotein

SR:

Scavenger receptors

STEMI:

ST-segment elevation myocardial infarction

TGF:

Transforming growth factor

TNF:

tumor necrosis factor

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Funding

This study was supported by the Ministry of Science and Technology of Taiwan grant MOST 103-2320-B-002-029-MY2.

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Authors and Affiliations

  1. Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Shwu-Fen Chang

  2. Department of Internal Medicine, Cardiovascular Center and Division of Cardiology, College of Medicine, National Taiwan university, Taipei, Taiwan

    Po-Yuan Chang

  3. Department of Biochemistry and Molecular Biology; College of Medicine, National Taiwan university, No. 1, Jen Ai Road Section 1, Taipei, 100233, Taiwan

    Yuan-Chun Chou & Shao-Chun Lu

Authors
  1. Shwu-Fen Chang
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Correspondence to Shao-Chun Lu.

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Chang, SF., Chang, PY., Chou, YC. et al. Electronegative LDL Induces M1 Polarization of Human Macrophages Through a LOX-1-Dependent Pathway. Inflammation 43, 1524–1535 (2020). https://doi.org/10.1007/s10753-020-01229-6

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