Inhibition of JAK2-STAT3 signaling contributes to the effects of egg yolk oil in ameliorating atopic dermatitis in pharmacological models

Atopic dermatitis (AD), also known as eczema, is a chronic skin disease. The frequency and prevalence of AD have steadily grown over the last several decades. Available drugs for treating AD have limitations. Egg yolk oil (EYO), a traditional Chinese medicinal material prepared from chicken egg yolk, was widely used for AD management in China. However, the mechanisms of action of EYO in treating AD are not fully understood. This study aimed to investigate the anti-AD effects and mechanisms of EYO.

Our results showed that 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. Mechanistically, EYO inhibited the activation of STAT3 (Tyr705 and Ser727) and the STAT3 upstream kinase Janus kinase 2 (Tyr1007/1008), in ear tissues of AD mice and TNF-α/IFN-γ-stimulated HaCaT cells. EYO downregulated mRNA levels of inflammatory genes (IL33, and IL6) and itch-related genes (TSLP and CXCL1), upregulated mRNA levels of skin barrier-related genes (TJP1 and CLDN1) that are transcriptionally regulated by STAT3 in AD cell and mouse models. To verify the involvement of STAT3 signaling in EYO's effects, we over-activated STAT3 in HaCaT cells by transducing STAT3C (A662C, N664C mutant), a constitutively active STAT3 variant, into the cells. Upon STAT3 over-activation, the anti-AD effects of EYO (0.05%, v/v) in TNF-α/IFN-γ-stimulated HaCaT cells were significantly attenuated. Specifically, the mRNA levels of skin barrier-related genes TJP1 and CLDN1 were decreased from 33.61% to 31.28% and 18.95% to 13.21%, respectively; the mRNA levels of the inflammatory gene IL33 and the itch-related gene TSLP were significantly lowered from 55.26% to 36.27% and 64.12% to 52.83%, respectively.

In summary, we for the first time found that EYO ameliorates AD-like symptoms in mouse and cell models; and suppression of JAK2-STAT3 signaling contributes to the mechanisms of action of EYO. This study provides pharmacological justifications for the clinical application of EYO in treating AD.