7-Oxo-cholesterol potentiates pro-inflammatory signaling in human M1 and M2 macrophages

Brigitta Buttari, Luca Segoni, Elisabetta Profumo, Daniela D'Arcangelo, Stefania Rossi, Francesco Facchiano, Rita Businaro, Luigi Iuliano, Rachele Rigano

Research output: Contribution to journalArticle

Abstract

Macrophages, the major cellular components of atherosclerotic plaques, consist of two main subsets: the pro-inflammatory, M1 or classically activated macrophages, and the anti-inflammatory, M2 or alternatively activated macrophages. The molecular and cellular mechanisms that orchestrate the macrophage polarization and activation that may play a role in plaque progression and stability are poorly understood. Recent studies suggest that oxysterols, oxidative stress-mediated cholesterol oxidation products that are abundant in atherosclerotic lesions, may affect macrophage biology. We investigated whether 7-oxo-cholesterol (7oxo-C) affected polarized human M1 and M2 macrophage phenotypes and functions. Monocyte-derived M1 and M2 macrophages were challenged with 7oxo-C and their phenotype analyzed using flow cytometric analysis, and their function via secretome profiling, the presence of endocytosis and matrix metalloproteinase-9 (MMP-9) release. 7oxo-C increased the expression of HLA-DR in M1 macrophages, and CD14 on M2 macrophages. The oxysterol also reduced CD16 expression on M1 macrophages, while reducing their endocytotic capability and increasing MMP- 9 secretion in M2 macrophages. Secretome profiling from cultured cell supernatants showed that 7oxo-C stimulated the production of key pro-atherogenic mediators involved in pro-inflammatory, pro-invasive and pro-angiogenic mechanisms both in M1 and M2 cells. Hypoxic conditions potentiated the effects of 7oxo-C on M1 and M2 cells. The ability of 7oxo-C to polarize macrophages toward a pro-inflammatory state represents a potentially novel mechanism by which oxidative stress can contribute to atherosclerotic lesion progression.

Original languageEnglish
Pages (from-to)130-137
Number of pages8
JournalBiochemical Pharmacology
Volume86
Issue number1
DOIs
Publication statusPublished - 2013

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Keywords

  • Atherosclerosis
  • Inflammation
  • Macrophages
  • Monocytes
  • Oxysterols

ASJC Scopus subject areas

  • Pharmacology
  • Biochemistry

Cite this

Buttari, B., Segoni, L., Profumo, E., D'Arcangelo, D., Rossi, S., Facchiano, F., Businaro, R., Iuliano, L., & Rigano, R. (2013). 7-Oxo-cholesterol potentiates pro-inflammatory signaling in human M1 and M2 macrophages. Biochemical Pharmacology, 86(1), 130-137. https://doi.org/10.1016/j.bcp.2013.04.008