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

23 Citations (Scopus)

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

Fingerprint

Macrophages
Cholesterol
Oxidative stress
Oxidative Stress
Phenotype
Macrophage Activation
Matrix Metalloproteinase 9
HLA-DR Antigens
Atherosclerotic Plaques
Endocytosis
Matrix Metalloproteinases
Monocytes
Cultured Cells
Anti-Inflammatory Agents
Chemical activation
Cells
Polarization

Keywords

  • Atherosclerosis
  • Inflammation
  • Macrophages
  • Monocytes
  • Oxysterols

ASJC Scopus subject areas

  • Pharmacology
  • Biochemistry

Cite this

7-Oxo-cholesterol potentiates pro-inflammatory signaling in human M1 and M2 macrophages. / Buttari, Brigitta; Segoni, Luca; Profumo, Elisabetta; D'Arcangelo, Daniela; Rossi, Stefania; Facchiano, Francesco; Businaro, Rita; Iuliano, Luigi; Rigano, Rachele.

In: Biochemical Pharmacology, Vol. 86, No. 1, 2013, p. 130-137.

Research output: Contribution to journalArticle

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, vol. 86, no. 1, pp. 130-137. https://doi.org/10.1016/j.bcp.2013.04.008
Buttari, Brigitta ; Segoni, Luca ; Profumo, Elisabetta ; D'Arcangelo, Daniela ; Rossi, Stefania ; Facchiano, Francesco ; Businaro, Rita ; Iuliano, Luigi ; Rigano, Rachele. / 7-Oxo-cholesterol potentiates pro-inflammatory signaling in human M1 and M2 macrophages. In: Biochemical Pharmacology. 2013 ; Vol. 86, No. 1. pp. 130-137.
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