Phytocannabinoids Reduce Inflammation of Primed Macrophages and Enteric Glial Cells: An In Vitro Study

Abstract

Intestinal inflammation is mediated by a subset of cells populating the intestine, such as enteric glial cells (EGC) and macrophages. Different studies indicate that phytocannabinoids could play a possible role in the treatment of inflammatory bowel disease (IBD) by relieving the symptoms involved in the disease. 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 macrophage cells and EGCs triggered to undergo inflammation with lipopolysaccharide (LPS). The anti-inflammatory effect of several phytocannabinoids was measured by their ability to reduce TNFα transcription and translation in J774A1 macrophages and to diminish S100B and GFAP secretion and transcription in EGCs. Our results demonstrate that THC at the lower concentrations tested exerted the most effective anti-inflammatory effect in both J774A1 macrophages and EGCs compared to the other phytocannabinoids tested herein. We then performed RNA-seq analysis of EGCs exposed to LPS in the presence or absence of THC or THC-COOH. Transcriptomic analysis of these EGCs revealed 23 differentially expressed genes (DEG) compared to the 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 affects the mTOR and RAR signaling pathway, while THC-COOH mainly affects the IL6 signaling pathway.

Role of Cannabinoids in Oral Cancer

“…The CB2 receptor exhibits a notable presence in peripheral organs that possess immunerelated functions, encompassing the spleen, tonsils, and thymus [55], in addition to being found in the lungs and testes [49]. The CB2 receptor is also present in immune cells, such as macrophages and leukocytes [56]. In terms of relative abundance, the CB2 receptor is found in decreasing order in tonsillar B cells > natural killer cells > monocytes and granulocytes > T4 lymphocytes > T8 lymphocytes [57].…”

Cannabinoids’ Role in Modulating Central and Peripheral Immunity in Neurodegenerative Diseases

“…Cannabichromene (CBC), CBG, THCA, and THC-COOH also showed anti-inflammatory effects in EGCs [ 240 ]. In addition, a positive correlation was found between S100B protein levels and the severity of motor symptoms in PD patients [ 241 ]. S100B protein expression in EGCs has been decreased by phytocannabinoids [ 240 ].…”