Cannabidiol induced apoptosis in T cell to treat autoimmune hepatitis

University Of South Carolina At Columbia, Columbia SC

Investigators

Linked publications & trials

Abstract

The plant Cannabis and its extracts have long been used to treat pain. However, their psychotropic effects[unreadable] have prevented their widespread use in medicine. Their effects have been attributed to activation of[unreadable] cannabinoid receptors, CB1 and CB2. CB1 are highly expressed in the CMS, while CB2 is exclusively[unreadable] expressed on immune cells. Recent studies from our lab have demonstrated for the first time that naturally[unreadable] occurring plant cannabinoid, cannabidiol (CBD), which is non-psychoactive, can induce apoptosis in immune[unreadable] cells and is very effective in the treatment of autoimmune hepatitis (AIM). In the current study, we will also[unreadable] test the central hypothesis that CBD induces apoptosis in T cells through death receptor and/or[unreadable] mitochondria! pathways which are responsible for causing immunosuppression. Our studies will address the[unreadable] mechanism by which CBD may serve as a therapeutic modality in the treatment of autoimmune diseases,[unreadable] specifically staphylococcal enterotoxin B (SEB) and ConA-induced hepatitis (CAM), considered to be[unreadable] experimental models for human AIM. Liver disease is a major cause of morbidity and mortality and also the[unreadable] prognosis is poor. In many liver diseases including viral hepatitis, AIM and alcoholic liver disease, activated T[unreadable] lymphocytes and macrophages appear to play an important role in liver damage. AIM is an inflammatory liver[unreadable] disease that is primarily triggered by T cells. To address the effect of CBD on hepatitis, we will pursue the[unreadable] following Aims: # 1: We will use of CB1, CB2, CB1/CB2 and VR1 knockout (KO) mice to address the role of[unreadable] CB1, CB2 and vanilloid receptors in signaling CBD-induced apoptosis in T lymphocytes. # 2: We will identify[unreadable] the mechanisms of CBD-induced apoptosis in immune cells in vitro and in vivo, specifically the role of death[unreadable] receptor pathway versus the mitochondrial pathway. # 3: Effect of CBD on SEB-specific V beta8+ T cells and[unreadable] SEB-induced AIM will be investigated. # 4: Use of CBD in treatment of Con A-induced hepatitis and liver[unreadable] injury will be tested. We will investigate the effects of CBD on T cells, NK cells and NKT cell functions and[unreadable] their ability to produce inflammatory cytokines. Whether the effect of CBD is mediated through cannabinoid[unreadable] or vanniloid receptors will be tested.Together, the proposed studies will help in identifying the mechanisms[unreadable] through which a plant derived non-psychoactive cannabinoid, CBD can be used to effectively treat[unreadable] autoimmune hepatitis and liver injury.[unreadable]