Marijuana-derived Δ-9-tetrahydrocannabinol suppresses Th1/Th17 cell-mediated delayed-type hypersensitivity through microRNA regulation

Abstract

Δ9-Tetrahydrocannabinol (THC) is one of the major bioactive cannabinoids derived from the Cannabis sativa plant and is known for its anti-inflammatory properties. Delayed-type hypersensitivity (DTH) is driven by proinflammatory T helper cells including the classic inflammatory Th1 lineage as well as the more recently discovered Th17 lineage. In the current study, we investigated whether THC can alter the induction of Th1/Th17 cells involved in mBSA-induced DTH response. THC treatment (20 mg/kg) of C57BL/6 mice with DTH caused decreased swelling and infiltration of immune cells at the site of antigen rechallenge. Additionally, THC treatment decreased lymphocyte activation as well as Th1/Th17 lineage commitment, including reduced lineage-specific transcription factors and cytokines. Interestingly, while DTH caused an overexpression of miR-21, which increases Th17 differentiation via SMAD7 inhibition, and downregulation of miR-29b, an IFN-γ inhibitor, THC treatment reversed this microRNA (miR) dysregulation. Furthermore, when we transfected primary cells from DTH mice with miR-21 inhibitor or miR-29b mimic, as seen with THC treatment, the expression of target gene message was directly impacted increasing SMAD7 and decreasing IFN-γ expression, respectively. In summary, the current study suggests that THC treatment during DTH response can simultaneously inhibit Th1/Th17 activation via regulation of microRNA (miRNA) expression.

Suppression of STAT3 Signaling by Δ9-Tetrahydrocannabinol (THC) Induces Trophoblast Dysfunction

“…However, most studies about chronic substance exposure are related to cigarette smoking [26], alcohol consumption [27] and cocaine addiction [28] while the hazards of chronic marijuana use especially the effects on trophoblast function and its potential mechanism of influencing pregnancy outcomes is not well researched. THC as one of the major bioactive cannabinoids, has been widely used to study the effects of marijuana on various physiology and pathology processes [29], thus we provided more insight into the effects of THC on the biological function of human trophoblasts and the potential mechanism underlying the influence of marijuana exposure on placental development during pregnancy.…”

Medical cannabis: Another piece in the mosaic of autoimmunity?

“…A matching effect is observed following treatment with O‐1966, a selective CB2R agonist causing a decrease in nuclear factor‐kappa B and nuclear factor of activated T‐cells accompanied by an increase in the percentage of regulatory T‐cells and IL‐10 secretion . Different murine models show similar results, with CBD, AEA, or THC treatment, resulting in a reduction in either IL‐2 or interferon‐gamma (IFN‐γ) mRNA expression, IFN‐γ secretion, T‐cell proliferation, suppressed activator protein‐1, nuclear factor of activated T‐cell, IL‐17, tumor necrosis factor‐α (TNF‐α), lymphocyte activation, and an increase in IL‐10 secretion …”

“…17 Different murine models show similar results, with CBD, AEA, or THC treatment, resulting in a reduction in either IL-2 or interferon-gamma (IFN-g) mRNA expression, IFN-g secretion, T-cell proliferation, suppressed activator protein-1, nuclear factor of activated T-cell, 18 IL-17, tumor necrosis factor-a (TNF-a), lymphocyte activation, and an increase in IL-10 secretion. 19,20 B-cells are also exemplified as a potential target for cannabinoid treatment. In an in vivo murine model, a single preventive treatment with CBD prior to ovalbumin stimulation results in a significant reduction in immunoglobulin M and immunoglobulin G ovalbumin-specific antibodies.…”

Use of Cannabinoids to Treat Acute Respiratory Distress Syndrome and Cytokine Storm Associated with Coronavirus Disease-2019

“…Studies from our laboratory over the past 2 decades as well as those from others have shown that cannabinoids including THC and cannabidiol (CBD) act as potent anti-inflammatory agents ( Lombard et al, 2007 ; Hegde et al, 2008 ; Hegde et al, 2010 ; Jackson et al, 2014a ; Rao et al, 2015 ; Sido et al, 2015c ; Sido 2016a ; Elliott et al, 2018 ; Al-Ghezi et al, 2019a ; Al-Ghezi 2019b ; Almogi-Hazan and Or, 2020 ; Mohammed et al, 2020a ; Nichols and Kaplan, 2020 ). In fact, based on our studies ( Hegde et al, 2008 ), CBD has been approved by FDA to treat autoimmune hepatitis as an orphan drug.…”