摘要
背景:太阳紫外线(UV)辐射是导致皮肤光损伤和致癌的一个因素,炎症失调是急性和慢性紫外线照射有害影响的一个关键机制。皮肤癌治疗的健康和经济负担是巨大的,为制定改进的光保护和光血预防分子策略创造了越来越迫切的需要。 方法:对文献数据库进行结构化检索,检索同行评审的研究文献,共检索到139篇文章,其中包括我们自己的文章,并在TLR4指导下进行了批判性评价。 目的:了解toll样受体4(tlr4)作为皮肤抗微生物防御、伤口愈合和皮肤肿瘤性炎症的关键调节因子的分子作用。本综述的重点是最近发表的证据,表明TLR4是皮肤光保护和癌症光血预防的一个新的分子靶点。 结果:累积实验证据表明,TLR4的药理和遗传拮抗作用抑制了紫外线诱导的炎症信号传导,包括在体外和体内观察到的皮肤NF-κB和AP-1应激信号的衰减。TLR4定向小分子药物拮抗剂[包括厄立托兰、(+)-纳洛酮、ST2825和瑞他维德]现已被鉴定为一类新的分子疗法。TLR4拮抗剂在临床前和临床发展的不同阶段调节调节TLR4依赖性炎症信号,这也可能有助于人体皮肤光损伤和光致癌。 结论:未来的研究应探讨局部TLR4拮抗剂与其他分子策略(包括防晒剂)联合应用对皮肤的光保护和光血预防作用。
关键词: TLR4,皮肤光损伤,紫外线照射,光致癌,药理学TLR4调制,再储存
Current Medicinal Chemistry
Title:TLR4-directed Molecular Strategies Targeting Skin Photodamage and Carcinogenesis
Volume: 25 Issue: 40
关键词: TLR4,皮肤光损伤,紫外线照射,光致癌,药理学TLR4调制,再储存
摘要: Background: Exposure to solar ultraviolet (UV) radiation is a causative factor in skin photodamage and carcinogenesis, and inflammatory dysregulation is a key mechanism underlying detrimental effects of acute and chronic UV exposure. The health and economic burden of skin cancer treatment is substantial, creating an increasingly urgent need for the development of improved molecular strategies for photoprotection and photochemoprevention.
Methods: A structured search of bibliographic databases for peer-reviewed research literature revealed 139 articles including our own that are presented and critically evaluated in this TLR4-directed review.
Objective: To understand the molecular role of Toll-like receptor 4 (TLR4) as a key regulator of skin anti-microbial defense, wound healing, and cutaneous tumorigenic inflammation. The specific focus of this review is on recent published evidence suggesting that TLR4 represents a novel molecular target for skin photoprotection and cancer photochemoprevention.
Results: Cumulative experimental evidence indicates that pharmacological and genetic antagonism of TLR4 suppresses UV-induced inflammatory signaling involving the attenuation of cutaneous NF-κB and AP-1 stress signaling observable in vitro and in vivo. TLR4-directed small molecule pharmacological antagonists [including eritoran, (+)-naloxone, ST2825, and resatorvid] have now been identified as a novel class of molecular therapeutics. TLR4 antagonists are in various stages of preclinical and clinical development for the modulation of dysregulated TLR4-dependent inflammatory signaling that may also contribute to skin photodamage and photocarcinogenesis in human populations.
Conclusion: Future research should explore the skin photoprotective and photochemopreventive efficacy of topical TLR4 antagonism if employed in conjunction with other molecular strategies including sunscreens.
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Cite this article as:
TLR4-directed Molecular Strategies Targeting Skin Photodamage and Carcinogenesis, Current Medicinal Chemistry 2018; 25 (40) . https://dx.doi.org/10.2174/0929867324666170828125328
DOI https://dx.doi.org/10.2174/0929867324666170828125328 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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