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Phytocannabinoids reduce inflammation of primed macrophages and enteric glial cells Critical review of the effect of phytocannabinoids on gut immune cells

ABSTRACT: In vitro study analyzed the putative-anti-inflammatory effect of nine-selected pure cannabinoids on enteric glial cells (EGC’s) triggered to undergo inflammation with lipopolysaccharide (LPS) . Our results demonstrate that THC at the lower concentrations tested exerted the most effective anti- inflammatory effect in EGC’s compared to other phytocannabinoids tested herein. We then performed RNA-seq analysis of EGC’s exposed to LPS in the presence or absence of THC or THC-COOH. Transcriptomic analysis of these EGC’s revealed 23 differentially expressed genes (DEG) compared to treatment with only LPS. Pretreatment with THC resulted in 26 DEG and THC-COOH 25 DEG. To evaluate biological pathways affected by the different phytocannabinoid treatments we used the Ingenuity platform. We show that THC treatment but not THC-COOH affected

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE240225 | GEO | 2023/09/26

REPOSITORIES: GEO

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Project description:HIV/SIV-associated periodontal disease (gingivitis/periodontitis) (PD) represents a major comorbidity affecting HIV patients on anti-retroviral therapy. Employing a systems biology approach, we report molecular changes underlying PD and its modulation by phytocannabinoids [delta-9-tetrahydrocannabinol (THC)] in uninfected and SIV-infected rhesus macaques (RMs) treated with vehicle (VEH/SIV) or THC (THC/SIV). VEH/SIV but not THC/SIV RMs showed significant enrichment of genes linked to anti-viral defense, interferon-beta, NFkB, RIG-1, and JAK-STAT signaling. We focused on the anti-microbial DUOX1 and immune activation marker IDO1 that were reciprocally regulated in gingiva of VEH/SIV RMs. Both proteins localized to the gingival epithelium and CD163+ macrophages, and showed differential expression in the gingiva of THC/SIV and VEH/SIV RMs. Additionally, inflammation-associated miR-21, miR-142-3p, miR-223, and miR-125a-5p showed significantly higher expression in the gingiva of VEH/SIV RMs. In human primary gingival epithelial cells, miR-125a-5p post-transcriptionally downregulated DUOX1 and THC inhibited IDO1 protein expression through a cannabinoid receptor-2 mediated mechanism. Interestingly, THC/SIV RMs showed relatively reduced plasma levels of kynurenine, kynurenate, and the neurotoxic quinolinate compared to VEH/SIV RMs. Most importantly, THC blocked HIV/SIV-induced depletion of Firmicutes and Bacteroidetes, and reduced Gammaproteobacteria abundance in saliva. Reduced IDO1 protein expression was associated with significantly (p<0.05) higher abundance of Prevotella, Lactobacillus (L. salivarius, L. buchneri, L. fermentum, L. paracasei, L. rhamnosus, L. johnsonii) and Bifidobacteria and reduced abundance of the pathogenic Porphyromonas cangingivalis and Porphyromonas macacae. These translational findings suggest that phytocannabinoids could help reduce gingival/systemic inflammation and salivary dysbiosis in ART naïve and treated HIV individuals.

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Phytocannabinoids reduce inflammation of primed macrophages and enteric glial cells Critical review of the effect of phytocannabinoids on gut immune cells

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