BACKGROUND:

Endothelin 1 (ET-1) has been reported to evoke histamine-independent pruritus in　mammals. However, its association with pruritus or inflammation of atopic dermatitis (AD) has not been clarified. We sought to investigate the role of ET-1 in the skin inflammation of AD.

METHODS:

To examine the role of ET-1 in AD, we investigated the expression of ET-1 and IL-25 in the skin of an AD mouse model and AD patients, and examined the mutual regulatory relationship between ET-1 and IL-25, one of the important cytokines in AD, using the human HaCaT keratinocyte cell line.

RESULTS:

We immunohistochemically confirmed the upregulation of ET-1 and IL-25 expression in the epidermis of both the AD mouse model and AD patients. In vitro, IL-25 upregulated ET-1 mRNA and protein expression in a concentration- and time-dependent fashion in HaCaT cells. This IL-25-induced ET-1 expression was inhibited by ERK1/2 or JNK inhibitor. In a reciprocal manner, ET-1 also induced IL-25 upregulation. The enhancing effect of ET-1 on IL-25 was inhibited by an endothelin A receptor antagonist, ERK1/2 inhibitor or p38 inhibitor, but not by an endothelin B receptor antagonist or JNK inhibitor.

CONCLUSION:

These findings suggest that mutual upregulation of ET-1 and IL-25 takes place in the epidermis in AD, which may be a future target for anti-pruritic agents. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.