Endocannabinoids enhance lipid synthesis and apoptosis of human sebocytes via cannabinoid receptor-2-mediated signaling

Nóra Dobrosi, Balázs I. Tóth, Georgina Nagy, Anikó Dózsa, Tamás Géczy, L. Nagy, Christos C. Zouboulis, Ralf Paus, László Kovács, T. Bíró

Research output: Contribution to journalArticle

77 Citations (Scopus)

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).

Original languageEnglish
Pages (from-to)3685-3695
Number of pages11
JournalFASEB Journal
Volume22
Issue number10
DOIs
Publication statusPublished - Oct 2008

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Cannabinoid Receptors
Endocannabinoids
Apoptosis
Lipids
Sebaceous Glands
Cell death
Skin
Cell Death
Genes
Cannabinoid Receptor CB2
Seborrheic Dermatitis
Peroxisome Proliferator-Activated Receptors
Cannabinoids
Acne Vulgaris
RNA Interference
Cell culture
Hair
Transcription Factors
Up-Regulation
Cell Culture Techniques

Keywords

  • Acne vulgaris
  • Cannabinoid receptor subtypes
  • Gene expression
  • Human sebaceous gland-derived SZ95 sebocytes
  • Peroxisome proliferator-activated receptor
  • Signal transduction

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology
  • Medicine(all)

Cite this

Endocannabinoids enhance lipid synthesis and apoptosis of human sebocytes via cannabinoid receptor-2-mediated signaling. / Dobrosi, Nóra; Tóth, Balázs I.; Nagy, Georgina; Dózsa, Anikó; Géczy, Tamás; Nagy, L.; Zouboulis, Christos C.; Paus, Ralf; Kovács, László; Bíró, T.

In: FASEB Journal, Vol. 22, No. 10, 10.2008, p. 3685-3695.

Research output: Contribution to journalArticle

Dobrosi, N, Tóth, BI, Nagy, G, Dózsa, A, Géczy, T, Nagy, L, Zouboulis, CC, Paus, R, Kovács, L & Bíró, T 2008, 'Endocannabinoids enhance lipid synthesis and apoptosis of human sebocytes via cannabinoid receptor-2-mediated signaling', FASEB Journal, vol. 22, no. 10, pp. 3685-3695. https://doi.org/10.1096/fj.07-104877
Dobrosi, Nóra ; Tóth, Balázs I. ; Nagy, Georgina ; Dózsa, Anikó ; Géczy, Tamás ; Nagy, L. ; Zouboulis, Christos C. ; Paus, Ralf ; Kovács, László ; Bíró, T. / Endocannabinoids enhance lipid synthesis and apoptosis of human sebocytes via cannabinoid receptor-2-mediated signaling. In: FASEB Journal. 2008 ; Vol. 22, No. 10. pp. 3685-3695.
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