Mutual upregulation of endothelin-1 and IL-25 in atopic dermatitis

M. K. Aktar, M. Kido-Nakahara, M. Furue, T. Nakahara

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66 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)846-854
Number of pages9
JournalAllergy: European Journal of Allergy and Clinical Immunology
Issue number7
Publication statusPublished - Jul 1 2015

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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