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J Invest Dermatol. 2018 Aug;138(8):1699-1706. doi: 10.1016/j.jid.2018.02.022. Epub 2018 Mar 6.

Endocannabinoid Tone Regulates Human Sebocyte Biology.

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Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Institute of Biochemistry and Molecular Medicine, National Centre of Competence in Research TransCure, University of Bern, Bern, Switzerland.
Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Italy.
Department of Pathology, Gyula Kenézy University Hospital, University of Debrecen, Debrecen, Hungary.
Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodore Fontane, Dessau, Germany.
Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. Electronic address:
Department of Pediatrics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.


We have previously shown that endocannabinoids (eCBs) (e.g., anandamide) are involved in the maintenance of homeostatic sebaceous lipid production in human sebaceous glands and that eCB treatment dramatically increases sebaceous lipid production. Here, we aimed to investigate the expression of the major eCB synthesizing and degrading enzymes and to study the effects of eCB uptake inhibitors on human SZ95 sebocytes, thus exploring the role of the putative eCB membrane transporter, which has been hypothesized to facilitate the cellular uptake and subsequent degradation of eCBs. We found that the major eCB synthesizing (N-acyl phosphatidylethanolamine-specific phospholipase D, and diacylglycerol lipase-α and -β) and degrading (fatty acid amide hydrolase, monoacylglycerol lipase) enzymes are expressed in SZ95 sebocytes and also in sebaceous glands (except for diacylglycerol lipase-α, the staining of which was dubious in histological preparations). eCB uptake-inhibition with VDM11 induced a moderate increase in sebaceous lipid production and also elevated the levels of various eCBs and related acylethanolamides. Finally, we found that VDM11 was able to interfere with the proinflammatory action of the TLR4 activator lipopolysaccharide. Collectively, our data suggest that inhibition of eCB uptake exerts anti-inflammatory actions and elevates both sebaceous lipid production and eCB levels; thus, these inhibitors might be beneficial in cutaneous inflammatory conditions accompanied by dry skin.

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