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Keratinocytes in atopic dermatitis express abundant ΔNp73 regulating thymic stromal lymphopoietin production via NF-κB.

Abstract：

BACKGROUND:Atopic dermatitis (AD) is a chronic inflammatory skin disease that often cannot be completely controlled by modern medicine. Since multiple factors are intricately involved in the pathogenesis of AD, wide-ranging research is required for further advancement of AD treatment. Epidermal keratinocytes are the forefront to the external environment and play a pivotal role in the initiation of immune reaction against exogenous invasion. OBJECTIVE:Thymic stromal lymphopoietin (TSLP) is a keratinocyte-derived cytokine that induces differentiation and activation of type 2 helper T cells and innate lymphoid cells, cardinal effectors in pathophysiology of AD. We previously reported that ΔNp63, a p53-related molecule, regulates the expression of TSLP receptors and suggested the entity of a potential TSLP autocrine loop in the AD epidermis. In this study, we further explored the significance of p53 family transcription factors in TSLP production from human keratinocytes. METHOD:Expression profile of p73, a p53-related molecule, was evaluated in human AD tissue by immunohistochemistry. In addition, the function of p73 in producing TSLP was investigated with in vitro cultured keratinocytes via molecular biological analysis. RESULTS:ΔNp73 was abundantly expressed in the AD epidermis and increased the release of TSLP via NF-κB activation. Furthermore, the Toll-like receptor 3 signal enhanced ΔNp73 expression and thereby induced TSLP expression. CONCLUSION:Our results indicate that ΔNp73 is an additional participant in the mechanism of TSLP production. Amending the aberrant state of keratinocytes, represented by overexpression of ΔNp73, can be a novel therapeutic target of AD.

journal_name

J Dermatol Sci

journal_title

Journal of dermatological science

authors

Kumagai A,Kubo T,Kawata K,Kamekura R,Yamashita K,Jitsukawa S,Nagaya T,Sumikawa Y,Himi T,Yamashita T,Ichimiya S

doi

10.1016/j.jdermsci.2017.06.017

subject

Has Abstract

pub_date

2017-11-01 00:00:00

pages

175-183

issue

eissn

0923-1811

issn

1873-569X

pii

S0923-1811(17)30779-X

journal_volume

pub_type

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Keratinocytes in atopic dermatitis express abundant ΔNp73 regulating thymic stromal lymphopoietin production via NF-κB.