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多价肽治疗湿疹的疗效

Resolution of Eczema with Multivalent Peptides.

作者信息

Eggink Laura L, Hoober J Kenneth

机构信息

Susavion Biosciences, Tempe, Arizona, USA.

出版信息

JID Innov. 2022 Jul 7;2(5):100142. doi: 10.1016/j.xjidi.2022.100142. eCollection 2022 Sep.

Abstract

The integrity of the skin is an important aspect of QOL. Whether caused by genetic deficiencies or environmental insults, disruption of the surface barrier allows irritants and allergens to penetrate the skin, which initiates inflammatory responses by immune cells that often lead to life-long allergies. In this study, eczema was induced on depilated mouse skin with topical lipopolysaccharide or a mixture of Staphylococcal enterotoxin B and an extract of house dust mites, which resulted in thickening of the epidermis, epidermal disruption, and abundant neutrophils in the dermis. Within 14 days of topical treatment with 1 μM svL4, a tetravalent peptide, neutrophils were absent, and the epidermis had returned to a normal morphology. The sequence of svL4 contains glutamine residues that serve as a cross-linking substrate for transglutaminase 2, which gains access to the skin surface where the epidermis becomes disrupted. In contrast, topical application of 1 μM svH1C, a peptide mimetic of sialic acid that lacks glutamine residues, or 1 μM dexamethasone was ineffective in restoring normal epidermal morphology. The data suggest that svL4 would be a powerful treatment for resolving severe eczema.

摘要

皮肤完整性是生活质量的一个重要方面。无论是由基因缺陷还是环境侵害引起,皮肤表面屏障的破坏都会使刺激物和过敏原穿透皮肤,进而引发免疫细胞的炎症反应,这常常会导致终身过敏。在本研究中,通过在脱毛小鼠皮肤上局部应用脂多糖或金黄色葡萄球菌肠毒素B与屋尘螨提取物的混合物来诱发湿疹,这导致了表皮增厚、表皮破损以及真皮中大量中性粒细胞浸润。在用1μM的四价肽svL4进行局部治疗的14天内,中性粒细胞消失,表皮恢复了正常形态。svL4的序列包含谷氨酰胺残基,可作为转谷氨酰胺酶2的交联底物,该酶可进入表皮破损处的皮肤表面。相比之下,局部应用1μM的缺乏谷氨酰胺残基的唾液酸模拟肽svH1C或1μM地塞米松在恢复正常表皮形态方面无效。数据表明,svL4将是治疗重度湿疹的有效方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38c5/9418603/aeacda0c9f9e/fx1.jpg

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