CB2 receptor-mediated effects of pro-inflammatory macrophages influence survival of cardiomyocytes

Heinemann JC, Duerr GD, Keppel K, Breitbach M, Fleischmann BK, Zimmer A, Wehner S, Welz A, Dewald O (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Life Sciences Elsevier

Book Volume: 138

Pages Range: 18-28

DOI: 10.1016/j.lfs.2014.11.027

Abstract

Aims The endocannabinoid system and cannabinoid receptor 2 (CB2 receptor) have been associated with modulation of inflammatory response and myocardial adaptation after ischemic injury. In order to elucidate CB2 receptor-related effects during cellular interactions, we investigated cardiomyocyte survival and macrophage function in vitro. Main methods Murine embryonic (eCM) and adult (CM) cardiomyocytes, murine macrophages (MO), and their subtypes M1 (M1-MO) and M2 (M2-MO) were derived from wildtype- (WT) and CB2 receptor-deficient (Cnr2^-/-) mice. Cells were cultured separately or in co-culture under normoxia or hypoxia (2% O2) and pro-inflammatory stimulation using interferon (IFN)γ. Besides immunohistochemistry, we also measured mRNA expression (Taqman®) and performed FACS-analysis of cardiomyocytes. Macrophage migration was assessed using Boyden chamber assay. Key findings We found a significant induction of CB2 receptor mRNA and protein in murine eCM as well as M1- and M2-MO in vitro following cultivation under hypoxia or stimulation with IFNγ. A significantly higher amount of apoptotic Cnr2^-/--CMs was found after incubation under hypoxia when compared to WT-CMs. We observed a significantly stronger migration potential in Cnr2^-/--M1-MOs towards the supernatant of apoptotic CM, than in corresponding WT-cells. Co-culture revealed a significantly higher loss of eCMs and induction of their apoptosis after cultivation with Cnr2^-/--M1-MOs. Production of TNF-α in M1-MOs was dependent on CB2 receptor stimulation by anandamide. Significance Our data provide novel insights into CB2 receptor-mediated protection of cardiomyocytes during hypoxia and pro-inflammatory stimulation. We show CB2 receptor-dependent effects on migration and function of M1-MOs in interaction with cardiomyocytes, thereby influencing their survival.

Authors with CRIS profile

Oliver Dewald

Involved external institutions

Universitätsklinikum Bonn

Germany (DE) Rheinische Friedrich-Wilhelms-Universität Bonn

Germany (DE)

How to cite

APA:

Heinemann, J.C., Duerr, G.D., Keppel, K., Breitbach, M., Fleischmann, B.K., Zimmer, A.,... Dewald, O. (2015). CB2 receptor-mediated effects of pro-inflammatory macrophages influence survival of cardiomyocytes. Life Sciences, 138, 18-28. https://doi.org/10.1016/j.lfs.2014.11.027

MLA:

Heinemann, Jan C., et al. "CB2 receptor-mediated effects of pro-inflammatory macrophages influence survival of cardiomyocytes." Life Sciences 138 (2015): 18-28.

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