Egg yolk oil ameliorates atopic dermatitis and inhibits STAT3 signaling

Background: Atopic dermatitis (AD) is a chronic inflammatory and allergic skin disease that affects about 30% of children and 10% of adults globally. Inflammation, skin barrier dysfunction and pruritus are the main characteristics of AD. Egg yolk oil (EYO), a traditional Chinese medicinal material prepared from chicken egg yolk, was widely used for AD management in China. However, the pharmacological mechanisms of EYO in treating AD are not fully understood.
Objectives: This study aimed to investigate the anti-AD effects and mechanisms of EYO.

Methods: A MC903-induced AD mouse model and a TNF-α/IFN-γ-stimulated HaCaT keratinocyte cell model were used to evaluate the anti-AD effects of EYO. Flow cytometry was used to examined the percentages of Tregs and Th2 cells in mouse splenocytes (SP) and lymphocytes. MTT assays were used to determine cell proliferation. Annexin V-FITC/PI double staining was used to detect cell apoptosis. Transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analyses were conducted to investigate the anti-AD mechanisms of EYO.

Results: EYO ameliorated MC903-induced AD-like symptoms in mice, evidenced by significantly reduced ear thickness and decreased frequency of scratching. EYO increased viability of, and suppressed apoptosis in, TNF-α/IFN-γ-stimulated HaCaT cells. Mechanistic studies revealed that EYO increased the proportion of Tregs while decreased the proportion of Th2 cells in SP and LN of AD mice. EYO lowered the protein levels of phospho-STAT3 (Tyr705) and phospho-STAT3 (Ser727) in ear tissues of AD mice. In TNF-α/IFN-γ-stimulated HaCaT cells, EYO inhibited the activation/phosphorylation of a STAT3 upstream kinase Janus kinase 2 (Tyr1007/1008), STAT3 (Tyr705) and STAT3 (Ser727), decreased the nuclear localization of STAT3, downregulated mRNA levels of inflammatory genes (IL33, TNF, and IL6) and itch-related genes (CXCL1, CXCL2 and TSLP), upregulated mRNA levels of skin barrier-related genes (FLG, TJP1 and CLDN1) that are transcriptionally regulated by STAT3. EYO upregulated protein levels of skin barrier-related proteins (filaggrin, ZO-1 and claudin-1) and downregulated the itch-related protein TSLP.

Conclusions: In the present study, we for the first time found that EYO ameliorates AD-like symptoms in mouse and cell models, and suppression of STAT3 signaling contributes to the underlying mechanisms. This study provides pharmacological justifications for the clinical application of EYO in treating AD.