Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes
Attila Oláh, … , Ralf Paus, Tamás Bíró
Attila Oláh, … , Ralf Paus, Tamás Bíró
Published July 25, 2014
Citation Information: J Clin Invest. 2014;124(9):3713-3724. https://doi.org/10.1172/JCI64628.
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Research Article Dermatology

Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

Abstract

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-κB 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.

Authors

Attila Oláh, Balázs I. Tóth, István Borbíró, Koji Sugawara, Attila G. Szöllõsi, Gabriella Czifra, Balázs Pál, Lídia Ambrus, Jennifer Kloepper, Emanuela Camera, Matteo Ludovici, Mauro Picardo, Thomas Voets, Christos C. Zouboulis, Ralf Paus, Tamás Bíró

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Figure 8

Antiinflammatory actions of CBD are coupled to A2a receptor-dependent upregulation of TRIB3 and subsequent inhibition of the P65-NF-κB signaling.

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Antiinflammatory actions of CBD are coupled to A2a receptor-dependent up...
(A) IL1B and IL6 mRNA expression following 5 μg/ml LPS treatment with or without 10 μM CBD (24-hour treatments started at the day 2 after the transfection). ***P < 0.001 compared with the corresponding CBD-free treatments. ###P < 0.001 compared with the SCR group receiving the same treatments. “siTRIB3a” and “siTRIB3b” mark 2 different siRNA constructs against TRIB3. (B) Western blot analysis of lysates of SZ95 sebocytes treated with 5 μg/ml LPS, 10 μM CBD, and 1 μM HC for 25 minutes. (C) Determination of the intracellular cAMP concentration following 1-hour CBD (10 μM) or vehicle treatment. Data are presented as mean ± SEM of 3 independent determinations. One additional experiment yielded similar results. (D and E) TRIB3 and TNFA mRNA expression following the indicated treatments (5 μg/ml LPS, 10 μM CBD, and 10 nM ZM). (A, D, and E) Data are presented using the ΔΔCT method; PPIA-normalized mRNA expression of the vehicle control was set as 1 (solid line). Data are expressed as mean ± SD of 3 independent determinations. One additional experiment yielded similar results. (C–E) **P < 0.01, ***P < 0.001. (F) Western blot analysis of lysates of SZ95 sebocytes treated with 5 μg/ml LPS, 10 μM CBD, and 100 nM ZM for 25 minutes. (B and F) Numbers on the OD row indicate the optical density of the P-IκBα and P-P65 bands normalized to the corresponding β-actin signals.