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Microarray and Pathway Analysis Reveal Distinct Mechanisms Underlying Cannabinoid-Mediated Modulation of LPS-Induced Activation of BV-2 Microglial Cells

ABSTRACT: Cannabinoids are known to exert immunosuppressive activities. However, the mechanisms which contribute to these effects are unknown. Using lipopolysaccharide (LPS) to activate BV-2 microglial cells, we examined how Δ9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, and cannabidiol (CBD) the non-psychoactive component, modulate the inflammatory response.

ORGANISM(S): Mus musculus

PROVIDER: GSE70689 | GEO | 2015/07/09

SECONDARY ACCESSION(S): PRJNA289374

REPOSITORIES: GEO

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Microarray and Pathway Analysis Reveal Distinct Mechanisms Underlying Cannabinoid-Mediated Modulation of LPS-Induced Activation of BV-2 Microglial Cells

Project description:Cannabinoids are known to exert immunosuppressive activities. However, the mechanisms which contribute to these effects are unknown. Using lipopolysaccharide (LPS) to activate BV-2 microglial cells, we examined how Δ9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, and cannabidiol (CBD) the non-psychoactive component, modulate the inflammatory response. Microarray analysis of genome-wide mRNA levels was performed using Illumina platform and the resulting expression patterns analyzed using the Ingenuity Pathway Analysis to identify functional subsets of genes, and the Ingenuity System Database to denote the gene networks regulated by CBD and THC.

2015-07-09 | E-GEOD-70689 | biostudies-arrayexpress

miRNA expression profiles and molecular networks in resting and LPS-activated BV-2 microglia - Effect of cannabinoids

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The effects of cannabinoids on gene expression in glioma cells

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Single-cell transcriptomics reveals the natural product cannabinoid rewires tumor microenvironment via inhibiting alternative activation of macrophage and synergizes with PD-1 blockade

Project description:Colorectal tumors often display a suppressive immune microenvironment that limits their response to immunotherapy. Here, we report that Cannabidiol, a natural non-psychoactive constituent of the cannabis plant, inhibits colorectal cancer progression by modulating the suppressive tumor microenvironment. Our single-cell transcriptome sequencing results showed that CBD inhibits M2-polarized macrophages while promoting M1-polarized macrophages, which restores the intrinsic antitumor properties of macrophages to inhibit tumor progression. Mechanistically, CBD inhibits alternative activation of macrophages by inhibiting PI3K-Akt signaling, which shifts cell metabolism from oxidative phosphorylation and fatty acid oxidation to glycolysis. Moreover, CBD-mediated macrophage plasticity enhanced the response to anti-PD1 immunotherapy in xenograft mice. Taken together, our study provides new insights into the antitumor effects of CBD.

2023-09-29 | GSE220635 | GEO

Effects of CBD on the glioma stem cell molecular signature

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Proteome-wide profiling using sample multiplexing of a human neuroblastoma SH-SY5Y cell line treated with cannabidiol (CBD) and tetrahydrocannabinol (THC)

Project description:Cannabis has been used throughout history for medicinal and recreational purposes. The most notable cannabinoids derived from these plants are cannabidiol (CBD) and tetrahydrocannabinol (THC). Although well studied for their therapeutic effects, and highly debated concerning their recreational use, the underlying mechanisms of their biological effects are poorly defined. Here we used isobaric tag-based sample multiplexed proteome profiling to investigate protein abundance differences in the human neuroblastoma SH-SY5Y cell line treated with CBD and THC. We highlighted significantly regulated proteins by each treatment and performed pathway classification and associated protein-protein interaction analysis. Our data suggest that these treatments may result in mitochondrial dysfunction and induce endoplasmic reticulum stress. This dataset can be mined further to investigate the potential role of CBD and THC in various biological and disease contexts and thus provide a foundation for future studies.

2023-12-28 | PXD038121 | Pride

Cannabinoid Modulation of Eukaryotic Initiation Factors (eIF2α and eIF2B1) and Behavioral Cross-Sensitization to Cocaine in Adolescent Rats

Project description:Reduced eukaryotic Initiation Factor 2 (eIF2)α phosphorylation (p-eIF2α) enhances protein synthesis, memory formation, and addiction-like behaviors. However, p-eIF2α has not been examined with regard to psychoactive cannabinoids and cross-sensitization. Here, we find that a cannabinoid receptor agonist (WIN 55,212-2 mesylate [WIN]) reduced p-eIF2α in vitro by upregulating GADD34 (PPP1R15A), the recruiter of protein phosphatase 1 (PP1). The induction of GADD34 was linked to ERK/CREB signaling and to CREB-binding protein (CBP)-mediated histone hyperacetylation at the Gadd34 locus. In vitro, WIN also upregulated eIF2B1, an eIF2 activator subunit. We next found that WIN administration in vivo reduced p-eIF2α in the nucleus accumbens of adolescent, but not adult, rats. By contrast, WIN increased dorsal striatal levels of eIF2B1 and ΔFosB among both adolescents and adults. In addition, we found cross-sensitization between WIN and cocaine only among adolescents. These findings show that cannabinoids can modulate eukaryotic initiation factors, and they suggest a possible link between p-eIF2α and the gateway drug properties of psychoactive cannabinoids.

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Genome-wide DNA methylation profiling reveals epigenetic changes in the rat nucleus accumbens associated with cross-generational effects of adolescent THC exposure

Project description:Drug exposure during critical periods of development is known to have lasting effects, increasing one’s risk for developing mental health disorders. Emerging evidence has also indicated the possibility for drug exposure to even impact subsequent generations. Our previous work demonstrated that adolescent exposure to Δ9-tetrahydrocannabinol (THC), the main psychoactive component of marijuana (Cannabis sativa), in a Long-Evans rat model affects reward-related behavior and gene regulation in the subsequent (F1) generation unexposed to the drug. Questions, however, remained regarding potential epigenetic consequences. In the current study, using the same rat model, we employed Enhanced Reduced Representation Bisulfite Sequencing to interrogate the epigenome of the nucleus accumbens, a key brain area involved in reward processing. This analysis compared 16 animals with parental-THC exposure and 16 without to characterize relevant systems-level changes in DNA methylation. We identified 1,027 differentially methylated regions (DMRs) associated with parental THC exposure in F1 adults, each represented by multiple CpGs. These DMRs fell predominantly within introns, exons, and intergenic intervals, while showing a significant depletion in gene promoters. From these, we identified a network of DMR-associated genes involved in glutamatergic synaptic regulation, which also exhibited altered mRNA expression in the nucleus accumbens. These data provide novel insight into drug-related cross-generational epigenetic effects, and serve as a useful resource for investigators to explore novel neurobiological systems underlying drug abuse vulnerability. Study consisted of a total of 32 F1 individuals (Long-Evan rats); 16 animals (8 female, 8 male) were offspring from THC-exposed parents, and the remaining 16 animals (8 female, 8 male) were offspring from saline-exposed parents ("controls"; "VEH-exposed").

2015-06-19 | E-GEOD-69984 | biostudies-arrayexpress

Cannabidiol Inhibits SARS-CoV-2 Replication through Induction of the Host ER Stress and Innate Immune Responses

Project description:The spread of SARS-CoV-2 and ongoing COVID-19 pandemic underscores the need for new treatments. Here we report that cannabidiol (CBD) inhibits infection of SARS-CoV-2 in cells and mice. CBD and its metabolite 7-OH-CBD, but not THC or other congeneric cannabinoids tested, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after viral entry, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD inhibits SARS-CoV-2 replication in part by up-regulating the host IRE1a RNase endoplasmic reticulum (ER) stress response and interferon signaling pathways. In matched groups of human patients from the National COVID Cohort Collaborative, CBD (100 mg/ml oral solution per medical records) had a significant negative association with positive SARS-CoV-2 tests. This study highlights CBD as a potential preventative agent for early-stage SARS-CoV-2 infection and merits future clinical trials. We caution against use of non-medical formulations including edibles, inhalants or topicals as a preventative or treatment therapy at the present time.

2022-01-20 | GSE168797 | GEO

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