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.
J Invest Dermatol. 2018 Aug;138(8):1699-1706. doi: 10.1016/j.jid.2018.02.022. Epub 2018 Mar 6.
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.
我们之前已经表明内源性大麻素（eCBs）（例如，花生四烯酸乙醇胺）参与了人体皮脂腺中稳态皮脂脂质产生的维持，并且 eCB 处理可显著增加皮脂脂质的产生。在这里，我们旨在研究主要的 eCB 合成和降解酶的表达，并研究 eCB 摄取抑制剂对人 SZ95 皮脂细胞的影响，从而探索假定的 eCB 膜转运体的作用，该转运体被假设为促进 eCB 的细胞摄取和随后的降解。我们发现，主要的 eCB 合成酶（N-酰基磷脂酰乙醇胺特异性磷脂酶 D，二酰基甘油脂肪酶-α 和 -β）和降解酶（脂肪酸酰胺水解酶，单酰基甘油脂肪酶）在 SZ95 皮脂细胞中表达，也在皮脂腺中表达（除了二酰基甘油脂肪酶-α，其在组织学制剂中的染色可疑）。用 VDM11 抑制 eCB 摄取会适度增加皮脂脂质的产生，同时还会升高各种 eCB 和相关酰基乙醇酰胺的水平。最后，我们发现 VDM11 能够干扰 TLR4 激活剂脂多糖的促炎作用。总之，我们的数据表明，抑制 eCB 摄取会发挥抗炎作用，并提高皮脂脂质的产生和 eCB 水平；因此，这些抑制剂在伴有皮肤干燥的皮肤炎症性疾病中可能是有益的。
