Ann Dermatol.  2021 Feb;33(1):26-36. 10.5021/ad.2021.33.1.26.

Keratinocytes-Derived Reactive Oxygen Species Play an Active Role to Induce Type 2 Inflammation of the Skin: A Pathogenic Role of Reactive Oxygen Species at the Early Phase of Atopic Dermatitis

• Choi DI
• Park JH
• Choi JY
• Piao M
• Suh MS
• Lee JB
• Yun SJ
• Lee SC

• KMID: 2510146
• DOI: http://doi.org/10.5021/ad.2021.33.1.26

Abstract

Background
Atopic dermatitis (AD) is characterized by chronic, relapsing skin inflammation (eczema) with itchy sensation. Keratinocytes, which are located at the outermost part of our body, are supposed to play important roles at the early phase of type 2 inflammation including AD pathogenesis.
Objective
The purpose of this study was to evaluate whether keratinocytes-derived reactive oxygen species (ROS) could be produced by the allergens or non-allergens, and the keratinocytes-derived ROS could modulate a set of biomarkers for type 2 inflammation of the skin.
Methods
Normal human epidermal keratinocytes (NHEKs) were treated with an allergen of house dust mites (HDM) or a non-allergen of compound 48/80 (C48/80). Then, biomarkers for type 2 inflammation of the skin including those for neurogenic inflammation were checked by reverse transcriptase-polymerase chain reaction and western immunoblot experiments.
Results
HDM or C48/80 was found to upregulate expression levels of our tested biomarkers, including type 2 T helper-driving pathway (KLK5, PAR2, and NF κ B), epithelial-cell-derived cytokines (thymic stromal lymphopoietin, interleukin [IL]-25, IL-33), and neurogenic inflammation (NGF, CGRP). The HDMor C-48/80-induced expression levels of the biomarkers could be blocked by an antioxidant treatment with 5 mM N-acetyl-cysteine. In contrast, pro-oxidant treatment with 1 mM H₂O₂ could upregulate expression levels of the tested biomarkers in NHEKs.
Conclusion
Our results reveal that keratinocytes-derived ROS, irrespective to their origins from allergens or non-allergens, have a potential to induce type 2 inflammation of AD skin.

Keyword

Atopic dermatitis; House dust mite; Keratinocytes; Reactive oxygen species; Type 2 inflammation of the skin