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

Shwu Fen Chang, Po Yuan Chang, Yuan Chun Chou, Shao Chun Lu

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1524-1535
Number of pages12
JournalInflammation
Volume43
Issue number4
DOIs
Publication statusPublished - Aug 1 2020

Keywords

  • Electronegative LDL
  • LOX-1
  • Macrophage polarization

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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