Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Phytocannabinoids Reduce Inflammation of Primed Macrophages and Enteric Glial Cells

Version 1 : Received: 9 August 2023 / Approved: 9 August 2023 / Online: 9 August 2023 (10:52:21 CEST)

A peer-reviewed article of this Preprint also exists.

Cohen, G.; Gover, O.; Schwartz, B. Phytocannabinoids Reduce Inflammation of Primed Macrophages and Enteric Glial Cells: An In Vitro Study. Int. J. Mol. Sci. 2023, 24, 14628. Cohen, G.; Gover, O.; Schwartz, B. Phytocannabinoids Reduce Inflammation of Primed Macrophages and Enteric Glial Cells: An In Vitro Study. Int. J. Mol. Sci. 2023, 24, 14628.

Abstract

Inflammatory bowel diseases (IBD) includes Crohn's disease and ulcerative colitis, are idiopathic chronic relapsing inflammatory disorders of the intestinal tract. Different studies indicate that phytocanna-binoids, could play a possible role in the treatment of IBD by relieving the symptoms involved in the dis-ease. Phytocannabinoids act through the endocannabinoid system, which is distributed throughout the mammalian body in the cells of the immune system and in the intestinal cells. Our in vitro study analyzed the putative-anti-inflammatory effect of nine-selected pure cannabinoids in J774A1 macrophages cells and enteric glial cells (EGC’s) triggered to undergo inflammation with lipopolysaccharide (LPS). The an-ti-inflammatory effect of several phytocannabinoids was measured by their ability to reduce TNF tran-scription and translation in J774A1 macrophages and to diminish S100B and GFAP secretion and tran-scription in EGC’s. Our results demonstrate that THC at the lower concentrations tested exerted the most effective anti- inflammatory effect in both J774A1 macrophages and EGC’s compared to the other phy-tocannabinoids 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 differ-entially expressed genes (DEG) compared to treatment with only LPS. Pretreatment with THC resulted in 26 DEG and pretreatment with THC-COOH resulted in 25 DEG. To evaluate which biological pathways were affected by the different phytocannabinoid treatments we used the Ingenuity platform. We show that THC treatment affected the mTOR and RAR signaling pathway while THC-COOH affected mainly the IL6 signaling pathway.

Keywords

Phytocannabinoids; J774A1 M1 macrophages; Enteric Glial Cells

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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