Activation of CB1R Promotes Lipopolysaccharide-Induced IL-10 Secretion by Monocytic Myeloid-Derived Suppressive Cells and Reduces Acute Inflammation and Organ Injury - Sorbonne Université Access content directly
Journal Articles Journal of Immunology Year : 2020

Activation of CB1R Promotes Lipopolysaccharide-Induced IL-10 Secretion by Monocytic Myeloid-Derived Suppressive Cells and Reduces Acute Inflammation and Organ Injury

Jérémie Joffre
Che-Chung Yeh
Erika Wong
Mayuri Thete
  • Function : Author
Fengyun Xu
  • Function : Author
Ivana Zlatanova
  • Function : Author
Elliot Lloyd
  • Function : Author
Lester Kobzik
Matthieu Legrand
Judith Hellman

Abstract

Cannabis sativa and its principal components, D9-tetrahydrocannabinol (D9-THC) and cannabidiol, are increasingly being used to treat a variety of medical problems, including inflammatory conditions. Although studies suggest that the endocannabinoid system has immunomodulatory properties, there remains a paucity of information on the effects of cannabinoids on immunity and on outcomes of infection and injury. We investigated the effects and mechanism(s) of action of cannabinoid receptor agonists, including D9-THC, on inflammation and organ injury in endotoxemic mice. Administration of D9-THC caused a dramatic early upregulation of plasma IL-10 levels, reduced plasma IL-6 and CCL-2 levels, led to better clinical status, and attenuated organ injury in endotoxemic mice. The anti-inflammatory effects of D9-THC in endotoxemic mice were reversed by a cannabinoid receptor type 1 (CB 1 R) inverse agonist (SR141716), and by clodronate-induced myeloid-cell depletion, but not by genetic invalidation or blockade of other putative D9-THC receptors, including cannabinoid receptor type 2, TRPV1, GPR18, GPR55, and GPR119. Although D9-THC administration reduced the activation of several spleen immune cell subsets, the anti-inflammatory effects of D9-THC were preserved in splenectomized endotoxemic mice. Finally, using IL-10-GFP reporter mice, we showed that blood monocytic myeloid-derived suppressive cells mediate the D9-THC-induced early rise in circulating IL-10. These results indicate that D9-THC potently induces IL-10, while reducing proinflammatory cytokines, chemokines, and related organ injury in endotoxemic mice via the activation of CB 1 R. These data have implications for acute and chronic conditions that are driven by dysregulated inflammation, such as sepsis, and raise the possibility that CB 1 R-signaling may constitute a novel target for inflammatory disorders.
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hal-04022847 , version 1 (10-03-2023)

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Jérémie Joffre, Che-Chung Yeh, Erika Wong, Mayuri Thete, Fengyun Xu, et al.. Activation of CB1R Promotes Lipopolysaccharide-Induced IL-10 Secretion by Monocytic Myeloid-Derived Suppressive Cells and Reduces Acute Inflammation and Organ Injury. Journal of Immunology, 2020, 204, pp.3339 - 3350. ⟨10.4049/jimmunol.2000213⟩. ⟨hal-04022847⟩
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