The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
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]
Citations
Cites
Green, D. R., & Reed, J. C. (1998) · Science · doi:10.1126/science.281.5381.1309 · Cited by 9,051
Peroxisome Proliferator-Activated Receptors: Nuclear Control of Metabolism
Desvergne, B., & Wahli, W. (1999) · Endocrine Reviews · doi:10.1210/edrv.20.5.0380 · Cited by 3,115
The Endocannabinoid System as an Emerging Target of Pharmacotherapy
Pacher, P., Bátkai, S., & Kunos, G. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.3.2 · Cited by 2,077
Roles of PPARs in health and disease
Kersten, S., Desvergne, B., & Wahli, W. (2000) · Nature · doi:10.1038/35013000 · Cited by 1,956
Role of Endogenous Cannabinoids in Synaptic Signaling
Freund, T. F., Katona, I., & Piomelli, D. (2003) · Physiological Reviews · doi:10.1152/physrev.00004.2003 · Cited by 1,616
Paus, R., & Cotsarelis, G. (1999) · New England Journal of Medicine · doi:10.1056/nejm199908123410706 · Cited by 1,438
Self-citationThe endocannabinoid system and its therapeutic exploitation
Marzo, V. D., Bifulco, M., & Petrocellis, L. D. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1495 · Cited by 1,090
Control of pain initiation by endogenous cannabinoids
Calignano, A., Rana, G. L., Giuffrida, A., & Piomelli, D. (1998) · Nature · doi:10.1038/28393 · Cited by 1,069
Chawla, A., Barak, Y., Nagy, L., Liao, D., Tontonoz, P., & Evans, R. M. (2001) · Nature Medicine · doi:10.1038/83336 · Cited by 1,069
Self-citationKarst, H., Berger, S., Turiault, M., Tronche, F., Schütz, G., & Joëls, M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507572102 · Cited by 774
Involvement of the endocannabinoid system in drug addiction
Maldonado, R. J., Valverde, O., & Berrendero, F. (2006) · Trends in Neurosciences · doi:10.1016/j.tins.2006.01.008 · Cited by 601
Ibrahim, M. M., Porreca, F., Lai, J., Albrecht, P. J., Rice, F. L., Khodorova, A., Davar, G., Makriyannis, A., Vanderah, T. W., Mata, H. P., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409888102 · Cited by 521
Cannabinoids go nuclear: evidence for activation of peroxisome proliferator‐activated receptors
O’Sullivan, S. E. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707423 · Cited by 509
Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors
Casanova, M., Blázquez, C., Martínez‐Palacio, J., Villanueva, C., Fernández‐Aceñero, M. J., Huffman, J. W., Jorcano, J. L., & Guzmán, M. (2003) · Journal of Clinical Investigation · doi:10.1172/jci16116 · Cited by 443
Toyoda, M., & Morohashi, M. (2001) · Medical Molecular Morphology · doi:10.1007/s007950100002 · Cited by 383
Establishment and Characterization of an Immortalized Human Sebaceous Gland Cell Line (SZ95)1
Zouboulis, C. C., Seltmann, H., Orfanos, C. E., & Neitzel, H. (1999) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.1999.00771.x · Cited by 363
Self-citationYoon, J. C., Chickering, T. W., Rosen, E. D., Dussault, B., Qin, Y., Soukas, A., Friedman, J. M., Holmes, W. E., & Spiegelman, B. M. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.14.5343-5349.2000 · Cited by 356
Regulation of Extracellular Signal-Regulated Kinase by Cannabinoids in Hippocampus
Derkinderen, P., Valjent, E., Toutant, M., Corvol, J., Enslen, H., Ledent, C. A., Trzăskos, J. M., Caboche, J., & Girault, J. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-06-02371.2003 · Cited by 350
What is the pathogenesis of acne?
Zouboulis, C. C., Eady, E. A., Philpott, M., Goldsmith, L. A., Orfanos, C. E., Cunliffe, W. C., & Rosenfield, R. L. (2005) · Experimental Dermatology · doi:10.1111/j.0906-6705.2005.0285a.x · Cited by 340
Self-citationAttenuation of Allergic Contact Dermatitis Through the Endocannabinoid System
Karsak, M., Gaffal, E., Date, R., Wang‐Eckhardt, L., Rehnelt, J., Petrosino, S., Starowicz, K., Steuder, R., Schlicker, E., Cravatt, B. F., et al. (2007) · Science · doi:10.1126/science.1142265 · Cited by 338
Ständer, S., Schmelz, M., Metze, D., Luger, T. A., & Rukwied, R. (2005) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2005.01.007 · Cited by 303
Cannabinoid receptors as novel targets for the treatment of melanoma
Blázquez, C., Carracedo, A., Barrado, L., Real, P. J., Fernández-Luna, J. L., Velasco, G., Malumbres, M., & Guzmán, M. (2006) · The FASEB Journal · doi:10.1096/fj.06-6638fje · Cited by 293
Corticotropin-releasing hormone: An autocrine hormone that promotes lipogenesis in human sebocytes
Zouboulis, C. C., Seltmann, H., Hiroi, N., Chen, W., Young, M., Oeff, M., Scherbaum, W. A., Orfanos, C. E., McCann, S. M., & Bornstein, S. R. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.102180999 · Cited by 290
Self-citationEndovanilloid signaling in pain
Marzo, V. D. (2002) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(02)00340-9 · Cited by 272
Wright, K. L., Duncan, M., & Sharkey, K. A. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707486 · Cited by 269
Alestas, T., Ganceviciene, R., Fimmel, S., Müller-Decker, K., & Zouboulis, C. C. (2006) · Journal of Molecular Medicine · doi:10.1007/s00109-005-0715-8 · Cited by 269
Self-citationThe Peroxisome Proliferator-activated Receptor δ Promotes Lipid Accumulation in Human Macrophages
Vosper, H., Patel, L., Graham, T. L., Khoudoli, G. A., Hill, A., Macphee, C. H., Pinto, I., Smith, S. A., Suckling, K. E., Wolf, C. R., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m108482200 · Cited by 268
Iodo-Resiniferatoxin, a New Potent Vanilloid Receptor Antagonist
Wahl, P., Foged, C., Tullin, S., & Thomsen, C. (2001) · Molecular Pharmacology · doi:10.1124/mol.59.1.9 · Cited by 261
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Bátkai, S., Osei‐Hyiaman, D., Pan, H., El-Assal, O. N., Rajesh, M., Mukhopadhyay, P., Hong, F., Harvey-White, J. D., Jafri, A., Haskó, G., et al. (2007) · The FASEB Journal · doi:10.1096/fj.06-7451com · Cited by 252
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Ozaita, A., Puighermanal, E., & Maldonado, R. J. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04642.x · Cited by 221
Zouboulis, C. C., Xia, L., Akamatsu, H., Seltmann, H., Fritsch, M., Hornemann, S., Rühl, R., Chen, W., Nau, H., & Orfanos, C. E. (1998) · Dermatology · doi:10.1159/000017861 · Cited by 216
Self-citationShappell, S. B., Gupta, R. A., Manning, S., Whitehead, R. H., Boeglin, W. E., Schneider, C. G., Case, T., Price, J. O., Jack, G. S., Wheeler, T. M., et al. (2001) · PubMed · Cited by 207
Cannabinoid Addiction: Behavioral Models and Neural Correlates
Maldonado, R. J., & de Fonseca, F. R. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-09-03326.2002 · Cited by 205
Rajesh, M., Mukhopadhyay, P., Haskó, G., Huffman, J. W., Mackie, K., & Pacher, P. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707569 · Cited by 198
The endocannabinoid system, anandamide and the regulation of mammalian cell apoptosis
Maccarrone, M., & Finazzi‐Agrò, A. (2003) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401284 · Cited by 195
A Hot New Twist to Hair Biology
Bodó, E., Bı́ró, T., Telek, A., Czifra, G., Griger, Z., Tóth, B. I., Mescalchin, A., Ito, T., Bettermann, A., Kovács, L., et al. (2005) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)62320-6 · Cited by 193
Self-citationCharacterization of Functional Vanilloid Receptors Expressed by Mast Cells
Bı́ró, T., Maurer, M., Modarres, S., Lewin, N. E., Brodie, C., Ács, G., Acs, P. I., Paus, R., & Blumberg, P. M. (1998) · Blood · doi:10.1182/blood.v91.4.1332 · Cited by 192
Self-citationPeroxisome Proliferator-Activated Receptors Increase Human Sebum Production
Trivedi, N. R., Cong, Z., Nelson, A. M., Albert, A. J., Rosamilia, L. L., Sivarajah, S., Gilliland, K. L., Liu, W., Mauger, D. T., Gabbay, R. A., et al. (2006) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700336 · Cited by 184
Cardiovascular Pharmacology of Cannabinoids
Pacher, P., Bátkai, S., & Kunos, G. (2005) · Springer eBooks · doi:10.1007/3-540-26573-2_20 · Cited by 169
The Endocannabinoid System in Human Keratinocytes
Maccarrone, M., Rienzo, M. D., Battista, N., Gasperi, V., Guerrieri, P., Rossi, A., & Finazzi‐Agrò, A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303994200 · Cited by 167
Neuroendocrine regulation of sebocytes – a pathogenetic link between stress and acne
Zouboulis, C. C., & Böhm, M. (2004) · Experimental Dermatology · doi:10.1111/j.1600-0625.2004.00254.x · Cited by 161
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Self-citationThe endocannabinoid system: a drug discovery perspective.
Piomelli, D. (2005) · PubMed · Cited by 152
PPARgamma regulates the function of human dendritic cells primarily by altering lipid metabolism.
Szatmári, I., Töröcsik, D., Agostini, M., Nagy, T., Gurnell, M., Barta, E., Chatterjee, K., & Nagy, L. (2007) · Blood · doi:10.1182/blood-2007-06-096222 · Cited by 144
Self-citationDifferentiation and Apoptosis in Human Immortalized Sebocytes
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Storr, M., & Sharkey, K. A. (2007) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2007.08.008 · Cited by 120
Celso, C. L., Berta, M., Braun, K. M., Frye, M., Lyle, S. R., Zouboulis, C. C., & Watt, F. M. (2008) · Stem Cells · doi:10.1634/stemcells.2007-0651 · Cited by 120
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Telek, A., Bı́ró, T., Bodó, E., Tóth, B. I., Borbíró, I., Kunos, G., & Paus, R. (2007) · The FASEB Journal · doi:10.1096/fj.06-7689com · Cited by 113
Self-citationBodó, E., Kovács, I., Telek, A., Varga, A., Paus, R., Kovács, L., & Bı́ró, T. (2004) · Journal of Investigative Dermatology · doi:10.1111/j.0022-202x.2004.23209.x · Cited by 112
Self-citationParadisi, A., Pasquariello, N., Barcaroli, D., & Maccarrone, M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m707964200 · Cited by 110
Zhang, Q., Seltmann, H., Zouboulis, C. C., & Konger, R. L. (2005) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700028 · Cited by 79
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Maccarrone, M., Fiorucci, L., Erba, F., Bari, M., Finazzi‐Agrò, A., & Ascoli, F. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01223-0 · Cited by 75
Matias, I., Vergoni, A. V., Petrosino, S., Ottani, A., Pocai, A., Bertolini, A., & Marzo, V. D. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2007.06.011 · Cited by 50
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Gancevičienė, R., Gražienë, V., Böhm, M., & Zouboulis, C. C. (2007) · Experimental Dermatology · doi:10.1111/j.1600-0625.2007.00565.x · Cited by 48
Self-citationPapp, H., Czifra, G., Bod�, E., L�z�r, J., Kov�cs, I., Aleksza, M., Juh�sz, I., Cs, P., Sipka, S., Kov�cs, L., et al. (2004) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-004-4014-2 · Cited by 46
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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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