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Endocannabinoids enhance lipid synthesis and apoptosis of human sebocytes via cannabinoid receptor‐2‐mediated signaling
Abstract
We had previously shown that both locally produced endocannabinoids and exocannabinoids, via cannabinoid receptor‐1 (CB1), are powerful inhibitors of human hair growth. To further investigate the role of the cannabinoid system in pilosebaceous unit biology, we have explored in the current study whether and how endocannabinoids have an impact on human sebaceous gland biology, using human SZ95 sebocytes as cell culture model. Here, we provide the first evidence that SZ95 sebocytes express CB2 but not CB1. Also, prototypic endocannabinoids (arachidonoyl ethanolamide/anandamide, 2‐arachidonoyl glycerol) are present in SZ95 sebocytes and dose‐dependently induce lipid production and (chiefly apoptosis‐driven) cell death. Endocannabinoids also up‐regulate the expression of key genes involved in lipid synthesis ( e.g. , PPAR transcription factors and some of their target genes). These actions are selectively mediated by CB2‐coupled signaling involving the MAPK pathway, as revealed by specific agonists/antagonists and by RNA interference. Because cells with “silenced” CB2 exhibited significantly suppressed basal lipid production, our results collectively suggest that human sebocytes utilize a paracrine‐autocrine, endogenously active, CB2‐mediated endocannabinoid signaling system for positively regulating lipid production and cell death. CB2 antagonists or agonists therefore deserve to be explored in the management of skin disorders characterized by sebaceous gland dysfunctions ( e.g. , acne vulgaris, seborrhea, dry skin).—Dobrosi, N., Tóth, B. I., Nagy, G., Dózsa, A., Géczy, T., Nagy, L., Zouboulis, C. C., Paus, R., Kovács, L., Bíró, T. Endocannabinoids enhance lipid synthesis and apoptosis of human sebocytes via cannabinoid receptor‐2‐mediated signaling. FASEB J. 22, 3685–3695 (2008)
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In the citing paper
“Although, sebocytes are able to alter their sebum production in response to different inflammatory stimuli42-45”
From Sebaceous-immunobiology is orchestrated by sebum lipids (2017) · cites this paper as [42]
In the citing paper
“Furthermore, sebocytes have also been identified as sources of various adipokines, such as adiponectin, interleukin (IL)-6, leptin, serpin E1, resistin and visfatin, within the skin”
From Sebaceous-immunobiology is orchestrated by sebum lipids (2017) · cites this paper as [42]
In the citing paper
“highlighting that sebaceous glands could represent a link between inflammation and lipid metabolism similarly to adipocytes.42,49”
From Sebaceous-immunobiology is orchestrated by sebum lipids (2017) · cites this paper as [42]
In the citing paper
“Recently Bíró et al. provided evidence that sebocytes express cannabinoid receptor-2”
From Sebaceous-immunobiology is orchestrated by sebum lipids (2017) · cites this paper as [42]
In the citing paper
“Endocannabinoids generally up-regulate the expression of genes involved in lipid synthesis, such as PPAR transcription factors”
From Sebaceous-immunobiology is orchestrated by sebum lipids (2017) · cites this paper as [42]
In the citing paper
“more interestingly arachidonoyl ethanolamide/anandamide, 2-arachidonoyl glycerol are also present in sebocytes and can induce lipid production and apoptosis.42”
From Sebaceous-immunobiology is orchestrated by sebum lipids (2017) · cites this paper as [42]
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Metadata
- Authors
- Dobrosi, N., Tóth, B. I., Nagy, G., Dózsa, A., Géczy, T., Nagy, L., Zouboulis, C. C., Paus, R., Kovács, L., & Bíró, T.
- Affiliations
- University of Debrecen (HU)
- Städtisches Klinikum Dessau (DE)
- University Hospital Schleswig-Holstein (DE)
- Department of Physiology University of Debrecen, Medical and Health Science Center, Research Center for Molecular Medicine Debrecen Hungary
- ORCID
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2008-07-02
- Volume
- 22
- Issue
- 10
- Pages
- 3685-3695
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2168147961
- Cited by
- 142
- References
- 63
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 9 · 2023: 6 · 2022: 8 · 2021: 7 · 2020: 14 · 2019: 5 · 2018: 11 · 2017: 13 · 2016: 11 · 2015: 7 · 2014: 5 · 2013: 6 · 2012: 8
- FWCI
- 5.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Dermatology › Acne and Rosacea Treatments and Effects
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Keywords
- endocannabinoids, sebocytes, CB2 receptor, lipogenesis, apoptosis, anandamide, 2-arachidonoylglycerol, peroxisome proliferator-activated receptors, MAPK signaling, sebaceous glands, pilosebaceous unit, acne, seborrhea, dry skin
- MeSH terms
- Cell Line, Epithelium, Gene Expression Regulation, Humans, Sebaceous Glands, Signal Transduction, Apoptosis, Mitogen-Activated Protein Kinases, RNA Interference, Receptor, Cannabinoid, CB1, Receptor, Cannabinoid, CB2, Lipogenesis, Cannabinoid Receptor Modulators, Endocannabinoids
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