Advanced Glycation End Products Promote Melanogenesis by Activating NLRP3 Inflammasome in Human Dermal Fibroblasts

被引:26
作者
Fang, Jiaqi [1 ]
Ouyang, Mengting [1 ]
Qu, Yingying [1 ]
Wang, Mengyao [1 ]
Huang, Xianyin [1 ]
Lan, Jingjing [1 ]
Lai, Wei [1 ]
Xu, Qingfang [1 ,2 ]
机构
[1] Sun Yat Sen Univ, Affiliated Hosp 3, Dept Dermatovenereol, Guangzhou, Peoples R China
[2] Sun Yat Sen Univ, Affiliated Hosp 3, Dept Dermatovenereol, 600 Tianhe Rd, Guangzhou 510630, Peoples R China
基金
中国国家自然科学基金;
关键词
NLRP3-INFLAMMASOME ACTIVATION; SIGNALING PATHWAY; KAPPA-B; INTERLEUKIN-18; EXPRESSION; RECEPTOR; ACCUMULATION; MELANOCYTES; INHIBITION; APOPTOSIS;
D O I
10.1016/j.jid.2022.03.025
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Advanced glycation end product (AGE) accumulation is significantly increased in the dermis of photoaged skin and plays crucial roles in photoaging. Although AGEs have been found to contribute to the yellowish discoloration of photoaged skin, their roles in photoaging-associated hyperpigmentation disorders have not been extensively studied. In this study, we observed that AGEs, NLRP3, and IL-18 were increased in the dermis of sun-exposed skin and lesions of melasma and solar lentigo and that dermal deposition of AGE was positively correlated with epidermal melanin levels. In addition, we found that AGE-BSA potently activated NLRP3 inflammasome and promoted IL-18 production and secretion in cultured fibroblasts, which was mediated by receptor for AGE/NF-KB pathway. Moreover, AGE-BSA significantly promoted melanogenesis by increasing tyrosinase activity and expression of microphthalmia-associated transcription factor and tyrosinase, which was dependent on NLRP3 inflammasome activation and IL-18 secretion in fibroblasts. Notably, AGE-collagen could activate NLRP3 inflammasome in fibroblasts and enhance melanogenesis. Furthermore, we found that IL-18 enhanced melanogenesis by binding to its receptor and activating p38 MAPK and extracellular signal-regulated kinase 1/2 signaling pathways in melanocytes. Importantly, the promelanogenesis of AGE-BSA was verified in ex vivo cultured skin and mouse models. These findings suggest that dermal AGEs stimulate melanogenesis and contribute to the development of photoaging-associated hyperpigmentation disorders.
引用
收藏
页码:2591 / +
页数:20
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