The synthetic cannabinoid WIN55,212-2 mesylate decreases the production of inflammatory mediators in rheumatoid arthritis synovial fibroblasts by activating CB2, TRPV1, TRPA1 and yet unidentified receptor targets
Rheumatoid arthritis (RA) is a very common chronic disease affecting many joints, most noticeably those in the hands and feet. It occurs when the body’s immune system attacks its own tissues that make up the joints, causing damage and consequently, pain. For example, synovial fibroblasts (SF) are cells that, in RA, secrete chemicals and proteins that destroy the joint-lining tissue called cartilage.
The endocannabinoid system is a signaling system that directly interacts with and regulates the human body’s immune cells. A lot of research has elucidated various mechanisms through which altering the activity of the endocannabinoid system helps control immune cells’ function and the resulting joint damage in RA. For instance, in the case of cartilage destruction by SF cells, a potent synthetic cannabinoid called WIN55,212-2 mesylate is found to significantly reduce all destructive chemicals and proteins secreted by SF at a wide spectrum of concentrations. Similar to naturally occurring cannabinoids, such as those extracted from marijuana, WIN55,212-2 mesylate binds to and activates the endocannabinoid system, with the highest affinity to the receptor CB2.
Interestingly, scientific findings suggest that at its high concentration, this compound activates both CB2 and another yet unknown receptor, both of which together are responsible for inhibiting SF. At its low concentration, such inhibitory effects however seem to result from WIN55,212-2 mesylate’s activation of 2 receptors in another family called transient receptor potential cation channels instead.
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