Bay 11-7082, an NF-κB Inhibitor, Prevents Post-Inflammatory Hyperpigmentation Through Inhibition of Inflammation and Melanogenesis.

IF 3.9 3区 医学 Q2 CELL BIOLOGY
Juwon Moon, Ik Jun Moon, Hoyong Hyun, Jae Min Yoo, Seung Hyun Bang, Youngsup Song, Sung Eun Chang
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引用次数: 0

Abstract

Post-inflammatory hyperpigmentation (PIH) is a very common disorder of cutaneous hyperpigmentation, which poses a persistent management challenge in the fields of dermatology and esthetics. This study was designed to explore the anti-melanogenic and anti-inflammatory effects of Bay 11-7082, an NF-κB inhibitor, using small-molecule screening, to determine its potential application for PIH prevention. The molecular mechanisms were investigated in vitro and ex vivo in epidermis-humanized mice using melanin content, RT-PCR, and immunoblotting. Bay 11-7082 suppressed proinflammatory cytokines and ameliorated 2,4-dinitrofluorobenzene (DNFB)-induced contact dermatitis on day 15. The suppression of melanin synthesis by Bay 11-7082 was attributed to the reduction of MITF, which was induced by extracellular signal-regulated kinase activation. Bay 11-7082 reduced epidermal melanin accumulation in UVB-stimulated ex vivo human epidermis as well as in the ear and tail skin of K14-stem cell factor (SCF) transgenic mice. Topical administration of Bay 11-7082 improved PIH on day 35 in the post-DNFB dorsal skin of K14-SCF transgenic mice. In conclusion, Bay 11-7082 can be considered a promising candidate for the development of a preventive topical agent for PIH.

NF-κB 抑制剂 Bay 11-7082 可通过抑制炎症和黑色素生成来预防炎症后色素沉着。
炎症后色素沉着(PIH)是一种非常常见的皮肤色素沉着疾病,在皮肤病学和美容领域一直是一个管理难题。本研究旨在通过小分子筛选,探索一种 NF-κB 抑制剂 Bay 11-7082 的抗黑色素生成和抗炎作用,以确定其在预防 PIH 方面的潜在应用。研究人员利用黑色素含量、RT-PCR 和免疫印迹技术,对表皮人源化小鼠的体外和体内分子机制进行了研究。Bay 11-7082抑制了促炎细胞因子,并在第15天改善了2,4-二硝基氟苯(DNFB)诱导的接触性皮炎。Bay 11-7082 抑制黑色素合成的原因是细胞外信号调节激酶活化诱导的 MITF 减少。Bay 11-7082 可减少 UVB 刺激的体外人体表皮以及 K14 干细胞因子(SCF)转基因小鼠耳部和尾部皮肤的表皮黑色素积累。外用 Bay 11-7082 在第 35 天改善了 K14-SCF 转基因小鼠 DNFB 后背侧皮肤的 PIH。总之,Bay 11-7082 可被视为开发 PIH 预防性局部用药的理想候选药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Pigment Cell & Melanoma Research
Pigment Cell & Melanoma Research 医学-皮肤病学
CiteScore
8.90
自引率
2.30%
发文量
54
审稿时长
6-12 weeks
期刊介绍: Pigment Cell & Melanoma Researchpublishes manuscripts on all aspects of pigment cells including development, cell and molecular biology, genetics, diseases of pigment cells including melanoma. Papers that provide insights into the causes and progression of melanoma including the process of metastasis and invasion, proliferation, senescence, apoptosis or gene regulation are especially welcome, as are papers that use the melanocyte system to answer questions of general biological relevance. Papers that are purely descriptive or make only minor advances to our knowledge of pigment cells or melanoma in particular are not suitable for this journal. Keywords Pigment Cell & Melanoma Research, cell biology, melatonin, biochemistry, chemistry, comparative biology, dermatology, developmental biology, genetics, hormones, intracellular signalling, melanoma, molecular biology, ocular and extracutaneous melanin, pharmacology, photobiology, physics, pigmentary disorders
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