Detailed characterization of the endocannabinoid system in human macrophages and foam cells, and anti-inflammatory role of type-2 cannabinoid receptor

Valerio Chiurchiù, Mirko Lanuti, Giuseppina Catanzaro, Filomena Fezza, Cinzia Rapino, Mauro Maccarrone

Research output: Contribution to journalArticle

Abstract

Objective: Cannabinoid receptors are activated in murine macrophages upon exposure to oxidized low-density lipoproteins (oxLDL), and type-1 cannabinoid receptor (CB1R) is considered as a risk factor in atherosclerosis, because it promotes cholesterol accumulation and release of inflammatory mediators. Conversely, accumulated evidence suggests a protective role for type-2 cannabinoid receptor (CB2R). Here, we sought to ascertain whether different elements of the endocannabinoid system (ECS) were activated in human lipid-laden macrophages, and whether CB2R played any role in atherogenesis and inflammation of these cells. Methods and results: Human macrophages were exposed to oxLDL in order to obtain lipid-laden foam cells. Liquid chromatography/mass spectrometry (LC/MS) was used to measure the production of the endocannabinoids in both macrophages and foam cells, and radiometric assays were performed to measure cannabinoid receptor binding and activity of endocannabinoid metabolizing enzymes. OxLDL accumulation was investigated by confocal imaging, and cytokine production and release were measured by means of flow cytometry and ELISA. The results showed that human macrophages possess a fully functional ECS, which was modulated by oxLDL. Selective CB2R activation reduced cellular oxLDL accumulation, which was associated with decreased expression of CD36 scavenger receptor, and decreased production of TNFα, IL-12 and IL-10. These anti-atherogenic and anti-inflammatory effects were reverted by the selective CB2R antagonist SR144528. Conclusions: A fully active ECS is present in human macrophages and macrophage-derived foam cells. Selective activation of CB2R reduces CD36-dependent oxLDL accumulation and modulates production of inflammatory cytokines, thus representing a potential therapeutic strategy to combat atherosclerosis.

Original languageEnglish
Pages (from-to)55-63
Number of pages9
JournalAtherosclerosis
Volume233
Issue number1
DOIs
Publication statusPublished - Mar 2014

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Cannabinoid Receptors
Endocannabinoids
Foam Cells
Anti-Inflammatory Agents
Macrophages
Atherosclerosis
Cytokines
Lipids
Scavenger Receptors
Interleukin-12
LDL Lipoproteins
Liquid Chromatography
Interleukin-10
oxidized low density lipoprotein
Mass Spectrometry
Flow Cytometry
Enzyme-Linked Immunosorbent Assay
Cholesterol
Inflammation
Enzymes

Keywords

  • Atherosclerosis
  • Cytokines
  • Endocannabinoid system
  • Inflammation
  • Low-density lipoproteins

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Detailed characterization of the endocannabinoid system in human macrophages and foam cells, and anti-inflammatory role of type-2 cannabinoid receptor. / Chiurchiù, Valerio; Lanuti, Mirko; Catanzaro, Giuseppina; Fezza, Filomena; Rapino, Cinzia; Maccarrone, Mauro.

In: Atherosclerosis, Vol. 233, No. 1, 03.2014, p. 55-63.

Research output: Contribution to journalArticle

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