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 language | English |
|---|---|
| Pages (from-to) | 130-137 |
| Number of pages | 8 |
| Journal | Biochemical Pharmacology |
| Volume | 86 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2013 |
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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 journal › Article
}
TY - JOUR
T1 - 7-Oxo-cholesterol potentiates pro-inflammatory signaling in human M1 and M2 macrophages
AU - Buttari, Brigitta
AU - Segoni, Luca
AU - Profumo, Elisabetta
AU - D'Arcangelo, Daniela
AU - Rossi, Stefania
AU - Facchiano, Francesco
AU - Businaro, Rita
AU - Iuliano, Luigi
AU - Rigano, Rachele
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Atherosclerosis
KW - Inflammation
KW - Macrophages
KW - Monocytes
KW - Oxysterols
UR - http://www.scopus.com/inward/record.url?scp=84884320029&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84884320029&partnerID=8YFLogxK
U2 - 10.1016/j.bcp.2013.04.008
DO - 10.1016/j.bcp.2013.04.008
M3 - Article
VL - 86
SP - 130
EP - 137
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
IS - 1
ER -