Resolution of Eczema with Multivalent Peptides

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.

Keywords: Ca2+, calcium ion; Dex, dexamethasone; HDM, house dust mite; KC, keratinocyte; LPS, lipopolysaccharide; SEB, Staphylococcal enterotoxin B; TGM, transglutaminase.