CB2 receptor-mediated effects of pro-inflammatory macrophages influence survival of cardiomyocytes
Copyright policy )CB2 receptor-mediated effects of pro-inflammatory macrophages influence survival of cardiomyocytes
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.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.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.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.
- Ludwig-Maximilians-Universität München Germany
- Drittes Physikalisches Institut Germany
- University of Bonn Germany
Cannabinoid Receptor Agonists, Inflammation, Mice, Knockout, Cell Survival, Tumor Necrosis Factor-alpha, Macrophages, Primary Cell Culture, Apoptosis, Coculture Techniques, Receptor, Cannabinoid, CB2, Interferon-gamma, Mice, Cell Movement, Animals, Myocytes, Cardiac
Cannabinoid Receptor Agonists, Inflammation, Mice, Knockout, Cell Survival, Tumor Necrosis Factor-alpha, Macrophages, Primary Cell Culture, Apoptosis, Coculture Techniques, Receptor, Cannabinoid, CB2, Interferon-gamma, Mice, Cell Movement, Animals, Myocytes, Cardiac
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