Anandamide reduces the migration of lymphocytes to the intestine by CB2 activation and reduces TNF-α in the target organs, protecting mice from graft-versus-host disease.

Autor: Berg BB; Graduate Program in Biological Sciences: Physiology and Pharmacology, Federal University of Minas Gerais, Belo Horizonte, Brazil., Linhares AFS; Graduate Program in Biological Sciences: Physiology and Pharmacology, Federal University of Minas Gerais, Belo Horizonte, Brazil., Martins DM; Federal University of Minas Gerais School of Medicine, Belo Horizonte, Brazil., Rachid MA; General Pathology Department, Federal University of Minas Gerais, Belo Horizonte, Brazil., Cau SBA; Department of Pharmacology, Federal University of Minas Gerais, Belo Horizonte, Brazil., Souza GG; Institute of Motricity Sciences, Federal University of Alfenas, Minas Gerais, Brazil., Carvalho JCS; Chemistry Department, Faculty of Philosophy Sciences and Letters of Ribeirão Preto, São Paulo, Brazil., Sorgi CA; Chemistry Department, Faculty of Philosophy Sciences and Letters of Ribeirão Preto, São Paulo, Brazil., Romero TRL; Department of Pharmacology, Federal University of Minas Gerais, Belo Horizonte, Brazil., Pinho V; Morphology Department, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil., Teixeira MM; Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, Brazil., Castor MGME; Department of Pharmacology, Federal University of Minas Gerais, Belo Horizonte, Brazil. Electronic address: marinacastor@ufmg.br.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2023 Oct 05; Vol. 956, pp. 175932. Date of Electronic Publication: 2023 Aug 01.
DOI: 10.1016/j.ejphar.2023.175932
Abstrakt: Graft-versus-host disease (GVHD) is a serious inflammatory illness that often occurs as a secondary complication of bone marrow transplantation. Current therapies have limited effectiveness and fail to achieve a balance between inflammation and the graft-versus-tumor effect. In this study, we investigate the effects of the endocannabinoid anandamide on the complex pathology of GVHD. We assess the effects of an irreversible inhibitor of fatty acid amine hydrolase or exogenous anandamide and find that they increase survival and reduce clinical signs in GVHD mice. In the intestine of GVHD mice, treatment with exogenous anandamide also leads to a reduction in the number of CD3 + , CD3 + CD4 + , and CD3 + CD8 + cells, which reduces the activation of CD3 + CD4 + and CD3 + CD8 + cells, as assessed by enhanced CD28 expression, a T cell co-stimulatory molecule. Exogenous AEA was also able to reduce TNF-α and increase IL-10 in the intestine of GVHD mice. In the liver, exogenous AEA reduces injury, TNF-α levels, and the number of CD3 + CD8 + cells. Interestingly, anandamide reduces Mac-1α, which lowers the adhesion of transplanted cells in mesenteric veins. These effects are mimicked by JWH133-a CB2 selective agonist-and abolished by treatment with a CB2 antagonist. Furthermore, the effects caused by anandamide treatment on survival were related to the CB2 receptor, as the CB2 antagonist abolished it. This study shows the critical role of the CB2 receptor in the modulation of the inflammatory response of GVHD by treatment with anandamide, the most prominent endocannabinoid.
Competing Interests: Declaration of competing interest The authors declare no competing financial interests.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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