Yu-Ping-Feng-San ameliorates recurrent allergic inflammation of atopic dermatitis by repairing tight junction defects of the epithelial barrier

Abstract

Background: Atopic dermatitis (AD) is a common allergic inflammatory skin disease, concomitant with a high relapse rate. Yu-Ping-Feng-San (YPFS), a well-known Chinese herbal decoction, reduces the AD relapse rate and recurring severity incidence. However, the underlying mechanism of YPFS on resisting AD recurrence is still unknown and further study is needed.

Purpose: To evaluate the effects of YPFS on recurrent allergic inflammation of AD in a murine model and to investigate the underlying mechanisms in vivo and ex vivo.

Methods: A fluorescein isothiocyanate (FITC)-induced AD relapsing mouse model was established to study the effects of YPFS and three active components, claycosin, formononetin, and cimifugin, on recurrent allergic inflammation in vivo. Histological analyses of ear tissue inflammation were evaluated by hematoxylin and eosin staining. Production of interleukin (IL)-4, IL-5, IL-13, and interferon-gamma in mice ear tissues, IgE in serum, and thymic stromal lymphopoietin (TSLP) in cell cultures were measured by ELISAs. Tight junction (TJ) expression was detected by immunohistochemistry and western blots. Epithelial barrier integrity was observed with electron microscopy, transepithelial electric resistance (TER), and paracellular flux measurements. HaCaT cells were utilized for ex vivo cellular analyses.

Results: In the recurrent phase of AD, YPFS exhibited both short- and long-term anti-allergic inflammatory efficacy with reduced ear tissue inflammation and decreased IL-4, IL-5, IL-13, and IgE production. The three active components, claycosin, formononetin, and cimifugin, showed similar effects as YPFS. Stimulus-induced decreased TER and increased FITC-dextran flux in air-liquid interface cultures of HaCaT cells were significantly repaired by YPFS and the three active components. Notably, the upregulated TJ (CLDN-1 and occludin) expression of epithelium was observed only with YPFS and the three components-treated mice as opposed to the result using conventional anti-allergy medicines. Restored TJ expression by YPFS three components was also detectable in the remission phase of AD. Moreover, decreased TJ expression influenced the effects of YPFS on epithelial cells-derived TSLP production.

Conclusions: YPFS ameliorated recurrent allergic inflammation of AD by repairing TJ defects of epithelial barriers. Intervening epithelial barrier functions could be a preventive and therapeutic approach for recurrent allergic inflammation of AD.

Keywords: Allergic inflammation relapse; Atopic dermatitis; Epithelial barrier; Tight junctions; Yu-Ping-Feng-San.