Inhibitory Effect of a Novel Non-Steroidal AMPamide on Inflammation and Sebogenesis by Suppressing TLR4 and TLR6-Mediated Signaling Pathway.

IF 3.2 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Biomolecules & Therapeutics Pub Date : 2025-09-01 Epub Date: 2025-08-06 DOI:10.4062/biomolther.2025.072
Myo Hyeon Park, Yu Ra Jung, Eun Bi Choi, Bu-Mahn Park, Jeonghwan Hwang, Miyoung Park
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引用次数: 0

Abstract

Seborrheic dermatitis (SD) is a chronic inflammatory skin disorder that primarily affects areas with increased sebaceous gland activity, and is characterized by erythematous scaly lesions. Malassezia utilizes sebum lipids to produce free fatty acids that may disrupt the epidermal barrier and trigger inflammation in eczematous lesions. However, the pathogenesis and mechanisms underlying the exaggerated inflammatory response and sebogenesis regulation in SD remain unknown. Activation of pattern recognition receptors, including Toll-like receptors (TLRs), is crucial for initiating innate immunity. In the present study, we evaluated the efficacy of a novel antimicrobial cosmetic ingredient, AMPamide, and elucidated its molecular mechanisms underlying the suppression of inflammation and sebogenesis in SD. Specifically, we investigated the inhibitory effect of AMPamide on TLR activation and its impact on downstream signaling pathways in LPS-stimulated HaCaT cells. The effects of AMPamide on lipid production and the expression of related regulatory factors in IGF-1-stimulated SZ95 sebaceous gland cells were also examined. These analyses were performed using RT-qPCR, western blotting, immunofluorescence staining, and Nile Red staining. AMPamide exhibited anti-inflammatory and skin barrier-strengthening effects by inhibiting TLR4/6 expression and multiple signaling pathways. Additionally, AMPamide attenuated lipid overproduction and the expression of related regulatory factors in IGF-1-stimulated SZ95 sebaceous gland cells. Therefore, the observed effects of AMPamide on LPS-stimulated human keratinocytes were mediated via blockade of the TLR-MyD88-MAPK and NF-κB signaling pathway. These results revealed that AMPamide may be a potential therapeutic agent for SD that inhibits TLR4/6 activation.

新型非甾体AMPamide通过抑制TLR4和tlr6介导的信号通路对炎症和皮脂生成的抑制作用
脂溢性皮炎(SD)是一种慢性炎症性皮肤病,主要影响皮脂腺活动增加的区域,其特征是红斑鳞状病变。马拉色菌利用皮脂产生游离脂肪酸,可能破坏表皮屏障并引发湿疹病变的炎症。然而,SD的过度炎症反应和脂脂生成调节的发病机制和机制尚不清楚。模式识别受体的激活,包括toll样受体(TLRs),对于启动先天免疫至关重要。在本研究中,我们评估了一种新型抗菌化妆品成分AMPamide的功效,并阐明了其抑制SD炎症和皮脂生成的分子机制。具体来说,我们研究了AMPamide对lps刺激的HaCaT细胞中TLR激活的抑制作用及其对下游信号通路的影响。AMPamide对igf -1刺激的SZ95皮脂腺细胞脂质生成及相关调节因子表达的影响也被检测。这些分析采用RT-qPCR、western blot、免疫荧光染色和尼罗红染色进行。AMPamide通过抑制TLR4/6的表达和多种信号通路,具有抗炎和皮肤屏障增强作用。此外,AMPamide可以减轻igf -1刺激的SZ95皮脂腺细胞中脂质过度产生和相关调节因子的表达。因此,AMPamide对lps刺激的人角质形成细胞的影响是通过阻断TLRs-MyD88-MAPK和NF-κB信号通路介导的。这些结果表明AMPamide可能是一种抑制TLR4/6激活的潜在SD治疗剂。
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来源期刊
CiteScore
6.60
自引率
8.10%
发文量
72
审稿时长
6-12 weeks
期刊介绍: Biomolecules & Therapeutics (Biomolecules & Therapeutics) (Print ISSN 1976-9148, Online ISSN 2005-4483) is an international, peer-reviewed, open access journal that covers pharmacological and toxicological fields related to bioactive molecules and therapeutics. It was launched in 1993 as "The Journal of Applied Pharmacology (ISSN 1225-6110)", and renamed "Biomolecules & Therapeutics" (Biomol Ther: abbreviated form) in 2008 (Volume 16, No. 1). It is published bimonthly in January, March, May, July, September and November. All manuscripts should be creative, informative, and contribute to the development of new drugs. Articles in the following categories are published: review articles and research articles.
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