Endocannabinoid Tone Regulates Human Sebocyte Biology

Nóra Zákány, Attila Oláh, Arnold Markovics, Erika Takács, Andrea Aranyász, Simon Nicolussi, Fabiana Piscitelli, Marco Allarà, Ágnes Pór, Ilona Kovács, Christos C. Zouboulis, Jürg Gertsch, Vincenzo Di Marzo, Tamás Bíró, Tamás Szabó

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Abstract

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.

Original languageEnglish
Pages (from-to)1699-1706
Number of pages8
JournalJournal of Investigative Dermatology
Volume138
Issue number8
DOIs
Publication statusPublished - Aug 2018

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Zákány, N., Oláh, A., Markovics, A., Takács, E., Aranyász, A., Nicolussi, S., Piscitelli, F., Allarà, M., Pór, Á., Kovács, I., Zouboulis, C. C., Gertsch, J., Di Marzo, V., Bíró, T., & Szabó, T. (2018). Endocannabinoid Tone Regulates Human Sebocyte Biology. Journal of Investigative Dermatology, 138(8), 1699-1706. https://doi.org/10.1016/j.jid.2018.02.022