Oxidized LDL enhances pro-inflammatory responses of alternatively activated M2 macrophages: A crucial role for Krüppel-like factor 2

Autor: L.J.H. van Tits, Anton F. H. Stalenhoef, Rinke Stienstra, Leo A. B. Joosten, Mihai G. Netea, P.L.E.M. van Lent
Rok vydání: 2011
Předmět:
Lipopolysaccharides
medicine.medical_specialty
Time Factors
Health aging / healthy living [IGMD 5]
medicine.medical_treatment
Adipose tissue macrophages
Macrophage-activating factor
Kruppel-Like Transcription Factors
Inflammation
Biology
Transfection
Downregulation and upregulation
Macrophages differentiation
Internal medicine
medicine
Humans
Macrophage
Secretion
Cells
Cultured
Chemokine CCL2
Foam cell
Oxidized LDL accumulation
Interleukin-6
Macrophage Colony-Stimulating Factor
Macrophages
Interleukin-8
Granulocyte-Macrophage Colony-Stimulating Factor
Krüppel-like factor 2
Macrophage Activation
Atherosclerosis
Infection and autoimmunity Auto-immunity
transplantation and immunotherapy [NCMLS 1]
Interleukin-10
Cell biology
Lipoproteins
LDL
Pathogenesis and modulation of inflammation [N4i 1]
Phenotype
Endocrinology
Cytokine
Cytokines
RNA Interference
Gene expression
Inflammation Mediators
medicine.symptom
Cardiology and Cardiovascular Medicine
Foam Cells
Zdroj: Atherosclerosis, 214, 2, pp. 345-9
Atherosclerosis, 214, 345-9
ISSN: 0021-9150
Popis: Contains fulltext : 97193.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Macrophages are key players in atherogenesis because of their properties to form foam cells that produce a large variety of pro-inflammatory mediators. We addressed the potency of phenotypic different macrophages to accumulate oxidized LDL. METHODS AND RESULTS: Surprisingly, anti-inflammatory M2 macrophages but not pro-inflammatory M1 macrophages rapidly accumulated oxidized LDL. Simultaneously, expression of Kruppel-like factor 2, a nuclear transcription factor known to suppress inflammation in endothelial cells and monocytes, decreased and the functional phenotype of M2 macrophages shifted towards a pro-inflammatory profile, characterized by higher production of IL-6, IL-8 and MCP-1 and lower expression of IL-10 upon stimulation with LPS. In contrast, Kruppel-like factor 2 expression and the phenotype of M1 macrophages remained largely unchanged upon oxidized LDL exposure. Downregulation of Kruppel-like factor 2 expression of M2 macrophages using siRNA technology led to a significant increase of LPS-induced MCP-1 secretion. CONCLUSIONS: We show that (1) anti-inflammatory M2 macrophages are more susceptible to foam cell formation than pro-inflammatory M1 macrophages, (2) exposure to oxidized LDL renders M2 macrophages pro-inflammatory, and (3) Kruppel-like factor 2 is involved in the enhanced secretion of MCP-1 by M2 macrophages loaded with oxidized LDL. The phenotype switch of M2 macrophages from an anti- to a pro-inflammatory profile may play an important role in pathogenesis of atherosclerosis, and could represent a novel therapeutic target.
Databáze: OpenAIRE
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