A20 ameliorates advanced glycation end products-induced melanogenesis by inhibiting NLRP3 inï¬ammasome activation in human dermal fibroblasts.
J Dermatol Sci
; 112(2): 71-82, 2023 Nov.
Article
in En
| MEDLINE
| ID: mdl-37741724
ABSTRACT
BACKGROUND:
Advanced glycation end products (AGEs) promote melanogenesis through activating NLRP3 inï¬ammasome in fibroblasts. Although A20 has been highlighted to inhibit NLRP3 inï¬ammasome activation, its roles and mechanisms remain elusive in photoaging-associated pigmentation.OBJECTIVES:
To determine the significance of fibroblast A20 in AGEs-induced NLRP3 inflammasome activation and pigmentation.METHODS:
The correlation between A20 and AGEs or melanin was studied in sun-exposed skin and lesions of melasma and solar lentigo. We then investigated A20 level in AGEs-treated fibroblast and the effect of fibroblast A20 overexpression or knockdown on AGEs-BSA-induced NLRP3 inflammasome activation and pigmentation, respectively. Finally, the severity of NLRP3 inflammasome activation and pigmentation was evaluated after mice were injected intradermally with A20-overexpression adeno-associated virus and AGEs-BSA.RESULTS:
Dermal A20 expression was decreased and exhibited negative correlation with either dermal AGEs deposition or epidermal melanin level in sun-exposed skin and pigmentary lesions. Moreover, both AGEs-BSA and AGEs-collagen robustly decreased A20 expression via binding to RAGE in fibroblasts. Further, A20 overexpression or depletion significantly decreased or augmented AGEs-BSA-induced activation of NF-κB pathway and NLRP3 inflammasome and IL-18 production and secretion in fibroblasts, respectively. Importantly, fibroblast A20 potently repressed AGEs-BSA-stimulated melanin contentï¼tyrosinase activityï¼and expression of microphthalmia-associated transcription factor and tyrosinase in melanocytes. Particularly, fibroblast A20 significantly abrogated AGEs-BSA-promoted melanogenesis in ex vivo skin and mouse models. Additionally, fibroblast A20 inhibited AGEs-BSA-activated MAPKs in melanocytes and the epidermis of ex vivo skin.CONCLUSIONS:
Fibroblast A20 suppresses AGEs-stimulate melanogenesis in photoaging-associated hyperpigmentation disorders by inhibiting NLRP3 inï¬ammasome activation.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Inflammasomes
/
NLR Family, Pyrin Domain-Containing 3 Protein
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
J Dermatol Sci
Journal subject:
DERMATOLOGIA
Year:
2023
Document type:
Article