THC decreases bone marrow-derived macrophage activation in a dose-dependent manner

Abstract

Abstract Macrophage activation is a major factor in progressive illnesses such as atherosclerosis, arthritis, and HIV-associated Neurological Disorder (HAND). Δ9-Tetrahydrocannabinol (THC), the main psychoactive compound found in cannabis, has been shown to have beneficial effects in treating these diseases, although the mechanism of action is not clear. Our lab and others have demonstrated the role of THC as an anti-inflammatory agent. In the current study, we attempted to investigate the effect of THC on macrophage activation. For this purpose, bone marrow was collected from tibia and femurs of C57BL/6 mice (10–12 weeks) and cells cultured in presence of macrophage colony stimulating factor (MCSF) for 4 days, in order to induce macrophage differentiation. On day 4, Lipopolysaccharide (LPS), gp120 of HIV or vehicle was added to the cultures and flow cytometry performed. Our results showed that THC treatment decreased F4/80+ macrophages in both LPS and gp120 groups in a dose-dependent manner when compared to vehicle-treated controls. MicroRNA-sequencing analysis showed a large number of miRs were dysregulated several fold. Importantly, there was an increase in the THC group of various miRNA such as miR-2137 and miR-486-5p that are involved in cell development and proliferation. Together, the role of THC in decreasing bone marrow-derived activated macrophages through miR dysregulation could provide new treatment strategies for diseases such as atherosclerosis, arthritis, and HAND. Supported by NIH grants P01AT003961, P20GM103641, R01ES030144, R01AI129788, R01AI123947 and R01AI160896