期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 124, 期 9, 页码 3713-3724出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI64628
关键词
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资金
- European Union [FP7-REGPOT-2008-1/229920]
- Belgian Federal Government [IUAP P7/13]
- Research Foundation-Flanders [G.0825.11]
- Research Council of the KU Leuven (PF-TRPLe)
- Italian Ministry of Health [RF-2010-2316435]
- Richter Talenturn Fellowship
- State of Hungary
- European Social Fund [TAMOP 4.2.4. A/2-11-1-2012-0001]
- People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7) under REA [330489]
- [LP2011-003/2013]
- [OTKA 101761]
- [OTKA 105369]
- [TAMOP-4.2.2./A-11/1/KONV-2012-0025]
The endocannabinoid system (ECS) regulates multiple physiological processes, including cutaneous cell growth and differentiation. Here, we explored the effects of the major nonpsychotropic phytocannabinoid of Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland function and determined that CBD behaves as a highly effective sebostatic agent. Administration of CBD to cultured human sebocytes and human skin organ culture inhibited the lipogenic actions of various compounds, including arachidonic acid and a combination of linoleic acid and testosterone, and suppressed sebocyte proliferation via the activation of transient receptor potential vanilloid-4 (TRPV4) ion channels. Activation of TRPV4 interfered with the prolipogenic ERK1/2 MAPK pathway and resulted in the downregulation of nuclear receptor interacting protein-1 (NRIP1), which influences glucose and lipid metabolism, thereby inhibiting sebocyte lipogenesis. CBD also exerted complex antiinflammatory actions that were coupled to A2a adenosine receptor-dependent upregulation of tribbles homolog 3 (TRIB3) and inhibition of the NF-kappa B signaling. Collectively, our findings suggest that, due to the combined lipostatic, antiproliferative, and antiinflammatory effects, CBD has potential as a promising therapeutic agent for the treatment of acne vulgaris.
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