Lesiak Agata, Paprocka Paulina, Wnorowska Urszula, Mańkowska Angelika, Król Grzegorz, Głuszek Katarzyna, Piktel Ewelina, Spałek Jakub, Okła Sławomir, Fiedoruk Krzysztof, Durnaś Bonita, Bucki Robert
Institute of Medical Science, Collegium Medicum, Jan Kochanowski University in Kielce, Kielce, Poland.
Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Białystok, Białystok, Poland.
Front Immunol. 2024 Dec 18;15:1502242. doi: 10.3389/fimmu.2024.1502242. eCollection 2024.
Acne vulgaris (AV) is a chronic inflammatory condition of the pilosebaceous units characterized by multiple immunologic, metabolic, hormonal, genetic, psycho-emotional dysfunctions, and skin microbiota dysbiosis. The latter is manifested by a decreased population (phylotypes, i.e., genetically distinct bacterial subgroups that play different roles in skin health and disease) diversity of the predominant skin bacterial commensal - . Like in other dysbiotic disorders, an elevated expression of endogenous antimicrobial peptides (AMPs) is a hallmark of AV. AMPs, such as human β-defensins, cathelicidin LL-37, dermcidin, or RNase-7, due to their antibacterial and immunomodulatory properties, function as the first line of defense and coordinate the host-microbiota interactions. Therefore, AMPs are potential candidates for pharmaceutical prophylaxis or treating this condition. This study outlines the current knowledge regarding the importance of AMPs in AV pathomechanism in light of recent transcriptomic studies. In particular, their role in improving the tight junctions (TJs) skin barrier by activating the fundamental cellular proteins, such as PI3K, GSK-3, aPKC, and Rac1, is discussed. We hypothesized that the increased expression of AMPs and their patterns in AV act as a compensatory mechanism to protect the skin with an impaired permeability barrier. Therefore, AMPs could be key determinants in regulating AV development and progression, linking acne-associated immune responses and metabolic factors, like insulin/IGF-1 and PI3K/Akt/mTOR/FoxO1 signaling pathways or glucotoxicity. Research and development of anti-acne AMPs are also addressed.
寻常痤疮（AV）是一种毛囊皮脂腺的慢性炎症性疾病，其特征为多种免疫、代谢、激素、遗传、心理情绪功能障碍以及皮肤微生物群失调。后者表现为主要皮肤共生细菌的种群（系统型，即在皮肤健康和疾病中发挥不同作用的基因不同的细菌亚群）多样性降低。与其他失调性疾病一样，内源性抗菌肽（AMPs）表达升高是寻常痤疮的一个标志。AMPs，如人β-防御素、杀菌肽LL-37、皮肤杀菌素或核糖核酸酶-7，由于其抗菌和免疫调节特性，作为第一道防线发挥作用，并协调宿主与微生物群的相互作用。因此，AMPs是预防或治疗这种疾病的潜在候选药物。本研究根据最近的转录组学研究概述了关于AMPs在寻常痤疮发病机制中的重要性的现有知识。特别讨论了它们通过激活基本细胞蛋白，如PI3K、GSK-3、非典型蛋白激酶C和Rac1，在改善紧密连接（TJs）皮肤屏障方面的作用。我们假设，AMPs在寻常痤疮中的表达增加及其模式作为一种补偿机制，用于保护通透性屏障受损的皮肤。因此，AMPs可能是调节寻常痤疮发展和进展的关键决定因素，将痤疮相关的免疫反应和代谢因素联系起来，如胰岛素/胰岛素样生长因子-1和PI3K/Akt/mTOR/FoxO1信号通路或糖毒性。本文还探讨了抗痤疮AMPs的研发情况。
