| Author | Rodrigues, Fernanda da Silva | |
| Author | Newton, William Robert | |
| Author | Tassinari, Isadora D'Ávila | |
| Author | Xavier, Felipe Henrique da Cunha | |
| Author | Marx, Adél | |
| Author | Fraga, Luciano Stürmer de | |
| Author | Wright, Karen | |
| Author | Guedes, Renata Padilha | |
| Author | Bambini Junior, Victorio | |
| Access date | 2024-07-29T14:22:53Z | |
| Available date | 2024-07-29T14:22:53Z | |
| Document date | 2024 | |
| Citation | RODRIGUES, Fernanda da Silva et al. Cannabidiol prevents LPS-induced inflammation by inhibiting the NLRP3 inflammasome and iNOS activity in BV2 microglia cells via CB2 receptors and PPARγ. Neurochemistry International: The Journal of Cellular and Molecular Neuroscience, v. 177, p. 1-12, July 2024. | |
| ISSN | 0197-0186 | |
| URI | https://www.arca.fiocruz.br/handle/icict/65201 | |
| Description | Produção científica do Laboratório de Pesquisa sobre o Timo. | pt_BR |
| Sponsorship | This study was funded by the Coordination for the Improvement of Higher Education Personnel (CAPES, Brazil). | |
| Sponsorship | Lancaster University (United Kingdom). | |
| Language | eng | en_US |
| Publisher | Elsevier | |
| Rights | restricted access | |
| Title | Cannabidiol prevents LPS-induced inflammation by inhibiting the NLRP3 inflammasome and iNOS activity in BV2 microglia cells via CB2 receptors and PPARγ | en_US |
| Type | Article | |
| DOI | 10.1016/j.neuint.2024.105769 | |
| Abstract | Neuroinflammation stands as a critical player in the pathogenesis of diverse neurological disorders, with microglial cells playing a central role in orchestrating the inflammatory landscape within the central nervous system. Cannabidiol (CBD) has gained attention for its potential to elicit anti-inflammatory responses in microglia, offering promising perspectives for conditions associated with neuroinflammation. Here we investigated whether the NLRP3 inflammasome and inducible nitric oxide synthase (iNOS) are involved in the protective effects of CBD, and if their modulation is dependent on cannabinoid receptor 2 (CB2) and PPARγ signalling pathways. We found that treatment with CBD attenuated pro-inflammatory markers in lipopolysaccharide (LPS)-challenged BV2 microglia in a CB2- and PPARγ-dependent manner. At a molecular level, CBD inhibited the LPS-induced pro-inflammatory responses by suppressing iNOS and NLRP3/Caspase-1-dependent signalling cascades, resulting in reduced nitric oxide (NO), interleukin-1β (IL-1β), and tumour necrosis factor-alpha (TNF-α) concentrations. Notably, the protective effects of CBD on NLRP3 expression, Caspase-1 activity, and IL-1β concentration were partially hindered by the antagonism of both CB2 receptors and PPARγ, while iNOS expression and NO secretion were dependent exclusively on PPARγ activation, with no CB2 involvement. Interestingly, CBD exhibited a protective effect against TNF-α increase, regardless of CB2 or PPARγ activation. Altogether, these findings indicate that CB2 receptors and PPARγ mediate the anti-inflammatory effects of CBD on the NLRP3 inflammasome complex, iNOS activity and, ultimately, on microglial phenotype. Our results highlight the specific components responsible for the potential therapeutic applications of CBD on neuroinflammatory conditions. | en_US |
| Affilliation | Universidade Federal de Ciências da Saúde de Porto Alegre. Porto Alegre, RS, Brasil / Lancaster University. Division of Biomedical and Life Sciences. Lancashire, Lancaster, United Kingdom. | |
| Affilliation | Lancaster University. Division of Biomedical and Life Sciences. Lancashire, Lancaster, United Kingdom / Exeter University. Medical Research Counsil Centre for Medical Mycology. Exeter, United Kingdom. | |
| Affilliation | Lancaster University. Division of Biomedical and Life Sciences. Lancashire, Lancaster, United Kingdom / Universidade Federal do Rio Grande do Sul. Instituto de Ciências Básicas da Saúde. Porto Alegre, RS, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Lancaster University. Division of Biomedical and Life Sciences. Lancashire, Lancaster, United Kingdom. | |
| Affilliation | Universidade Federal do Rio Grande do Sul. Instituto de Ciências Básicas da Saúde. Porto Alegre, RS, Brasil. | |
| Affilliation | Lancaster University. Division of Biomedical and Life Sciences. Lancashire, Lancaster, United Kingdom. | |
| Affilliation | Universidade Federal de Ciências da Saúde de Porto Alegre. Porto Alegre, RS, Brasil. | |
| Affilliation | Lancaster University. Division of Biomedical and Life Sciences. Lancashire, Lancaster, United Kingdom. | |
| Subject | Cannabidiol | en_US |
| Subject | Microglia | en_US |
| Subject | Neuroinflammation | en_US |
| Subject | NLRP3 | en_US |
| Subject | Inflammasome | en_US |
| Subject | iNOS | en_US |
| e-ISSN | 1872-9754 | |
