Estrogen Receptor Alpha Gene (ESR1) Facilitates Th2-immune Response and Enhances Th2 Cytokines in Experimental Atopic Dermatitis Mice

Molecular markers are involved in atopic dermatitis (AD) pathogenesis. The estrogen receptor (ESR)-1 gene, encoding ERα, is reported to express aberrantly in AD patients. To detect the biological functions of ESR1 in 2,4 dinitrochlorobenzene (DNCB)-treated mice. The DNCB-treated mice received a topical application of emulsion containing the 1,3-bis(4 hydroxyphenyl)-4-methyl-5-[4-(2-piperidinyl ethoxy) phenol]-1H-pyrazole dihydrochloride (MPP; an ESR1-selective antagonist) to dorsal skins and ears. Then the dermatitis scores, histopathological changes, and cytokine levels were evaluated. MPP specifically downregulated ESR1 expression in DNCB-applied mice. Functionally, application of MPP abolished the DNCB-induced promotion in dermatitis score. Additionally, MPP administration protected against DNCB-induced dermatitis severity, suppressed mast cell infiltration and reduced production of immunoglobulin E (IgE) and thymus and activation-regulated chemokine (TARC). Moreover, MPP treatment inhibited DNCB- induced production of Th2 cytokines and infiltration of CD4+ T cells. ESR1 facilitates Th2-immune response and enhances Th2 cytokines in AD mice.