Abstract

The incidence of atopic dermatitis (AD), a disease characterized by an abnormal immune balance and skin barrier function, has increased rapidly in developed countries. This study investigated the anti-atopic effect of Lithospermum erythrorhizon (LE) using NC/Nga mice induced by 2,4-dinitrochlorobenzene. LE reduced AD clinical symptoms, including inflammatory cell infiltration, epidermal thickness, ear thickness, and scratching behavior, in the mice. Additionally, LE reduced serum IgE and histamine levels, and restored the T helper (Th) 1/Th2 immune balance through regulation of the IgG1/IgG2a ratio. LE also reduced the levels of AD-related cytokines and chemokines, including interleukin (IL)-1β, IL-4, IL-6, tumor necrosis factor-α (TNF-α), thymic stromal lymphopoietin, thymus and activation-regulated chemokine, macrophage-derived chemokine, regulated on activation, normal T cell expressed and secreted, and monocyte chemoattractant protein-1 in the serum. Moreover, LE modulated AD-related cytokines and chemokines expressed and secreted by Th1, Th2, Th17, and Th22 cells in the dorsal skin and splenocytes. Furthermore, LE restored skin barrier function by increasing pro-filaggrin gene expression and levels of skin barrier-related proteins filaggrin, involucrin, loricrin, occludin, and zonula occludens-1. These results suggest that LE is a potential therapeutic agent that can alleviate AD by modulating Th1/Th2 immune balance and restoring skin barrier function.

Highlights

  • Atopic dermatitis (AD) is most common in early childhood, it is present in adults [1]

  • We found that Lithospermum erythrorhizon (LE) had a dose-dependent effect on the serum levels of monocyte chemoattractant protein-1 (MCP-1) as well as MCP-1 and Th2-mediated cytokines IL-4, IL-5, IL-13, and IL-31 secreted by splenocytes (Figures 6H and 7A,C)

  • LE reduces the levels of AD-related cytokines and chemokines in the serum and restores the Th1/Th2 immune balance via regulation of IgG1 and IgG2a

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Summary

Introduction

Atopic dermatitis (AD) is most common in early childhood, it is present in adults [1]. An important feature of AD is the differentiation of biased T helper (Th) 2 cells [9]; the increase in levels of Th2-mediated cytokines and chemokines causes a Th1/Th2 immune imbalance and impairs skin barrier function [6,10,11,12]. Th2 cell activation increases the expression and release of cytokines such as interleukin (IL)-4, IL-5, IL-13, and IL-31 [9]. Th1-mediated cytokines, including IL-12 and interferon-γ (IFN-γ), are downregulated resulting in Th1/Th2 immune imbalance. A biological response modulator, is released from degranulated mast cells and functions together with IgE to cause itching [5,18]. IL-31 impairs the skin barrier function by causing itching and inhibiting apoptosis in eosinophils [19,20,21]

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