Effective inhibition of Th17/Th22 pathway in 2D and 3D human models of psoriasis by Celastrol enriched plant cell culture extract.
Journal
Journal of the European Academy of Dermatology and Venereology : JEADV
ISSN: 1468-3083
Titre abrégé: J Eur Acad Dermatol Venereol
Pays: England
ID NLM: 9216037
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
07
11
2019
accepted:
03
04
2020
entrez:
13
8
2020
pubmed:
13
8
2020
medline:
30
4
2021
Statut:
ppublish
Résumé
Psoriasis is an immune-mediated inflammatory disease in which the Th17 pathway is mainly involved. Systemic interventions with biologics that specifically block the Th17 pathway are effective to treat severe psoriasis. However, for efficient topical treatment, small molecules are more suitable than antibodies to penetrate and target epidermal keratinocytes, the key players in psoriasis. Celastrol, a well-described triterpene, is present in low amounts in Tripterygium wilfordii roots. By using plant cell culture (PCC), we were able to boost Celastrol production in bioreactors. Here, we evaluated immune modulator effect of Celastrol enriched extract (CEE) in Th17/Th22 psoriasis induced in 2D and 3D human models in vitro in view of its dermatological usage. Human CD4 In 2D stimulated models (hCD4 and NHEK), CEE dose dependently inhibited, respectively, the expression of Th17 cytokines and psoriasis induced biomarkers. In 3D models (RHE and micro-epidermis), IL-8 expression was significantly reduced (RHE) and native phenotype was restored by CEE (micro-epidermis). These results clearly showed that Th17/Th22 cytokines, main inflammatory parameters, and psoriasis associated key biomarkers were inhibited by CEE in both 2D and 3D human in vitro models. Therefore, skin homeostasis could be restored by these modulator effects. Moreover, this high added value CEE was obtained by an ecofriendly bioprocess in contrast to traditional roots extracts. This is the first time that a well-defined CEE immune modulator has been proposed for psoriasis adjuvant care to reduce inflammation.
Sections du résumé
BACKGROUND
BACKGROUND
Psoriasis is an immune-mediated inflammatory disease in which the Th17 pathway is mainly involved. Systemic interventions with biologics that specifically block the Th17 pathway are effective to treat severe psoriasis. However, for efficient topical treatment, small molecules are more suitable than antibodies to penetrate and target epidermal keratinocytes, the key players in psoriasis. Celastrol, a well-described triterpene, is present in low amounts in Tripterygium wilfordii roots. By using plant cell culture (PCC), we were able to boost Celastrol production in bioreactors. Here, we evaluated immune modulator effect of Celastrol enriched extract (CEE) in Th17/Th22 psoriasis induced in 2D and 3D human models in vitro in view of its dermatological usage.
METHODS
METHODS
Human CD4
RESULTS
RESULTS
In 2D stimulated models (hCD4 and NHEK), CEE dose dependently inhibited, respectively, the expression of Th17 cytokines and psoriasis induced biomarkers. In 3D models (RHE and micro-epidermis), IL-8 expression was significantly reduced (RHE) and native phenotype was restored by CEE (micro-epidermis).
CONCLUSION
CONCLUSIONS
These results clearly showed that Th17/Th22 cytokines, main inflammatory parameters, and psoriasis associated key biomarkers were inhibited by CEE in both 2D and 3D human in vitro models. Therefore, skin homeostasis could be restored by these modulator effects. Moreover, this high added value CEE was obtained by an ecofriendly bioprocess in contrast to traditional roots extracts. This is the first time that a well-defined CEE immune modulator has been proposed for psoriasis adjuvant care to reduce inflammation.
Substances chimiques
Cytokines
0
Pentacyclic Triterpenes
0
Plant Extracts
0
Triterpenes
0
celastrol
L8GG98663L
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3-9Informations de copyright
© 2020 European Academy of Dermatology and Venereology.
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