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Updated: Apr 14, 2026
Cultivating a Three-dimensional Reconstructed Human Epidermis at a Large Scale
Published on: May 28, 2021
Mutual upregulation of endothelin-1 and IL-25 in atopic dermatitis
M K Aktar1, M Kido-Nakahara1, M Furue1,2
1Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
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 patients with AD 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 patients with AD. 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 of AD, which may be a future target for antipruritic agents.
