The inhibitory effect of A20 on the inflammatory reaction of epidermal keratinocytes

A20 is a negative regulator of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling, and has been implicated in the pathogenesis of psoriasis through genome-wide association study (GWAS). In the present study, we investigated the putative role of A20 in epidermal keratinocyte...

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Published in:International journal of molecular medicine 2016-04, Vol.37 (4), p.1099-1104
Main Authors: SOHN, KYUNG-CHEOL, BACK, SEUNG JU, CHOI, DAE-KYOUNG, SHIN, JUNG-MIN, KIM, SUE JEONG, IM, MYUNG, LEE, YOUNG, SEO, YOUNG-JOON, YOON, TAE-JIN, LEE, YOUNG HO, LEE, JEUNG-HOON, KIM, CHANG DEOK
Format: Article
Language:English
Subjects:
A20
Apoptosis
Cell culture
Cellular proteins
Cytokines
Disease
Disease susceptibility
Fibroblasts
Genetic aspects
Growth factors
Health aspects
Inflammation
inflammatory reaction
Keratinocytes
NF-κB
Pathogenesis
Proteins
Psoriasis
Skin
Skin diseases
Tumor necrosis factor-TNF
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Summary:A20 is a negative regulator of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling, and has been implicated in the pathogenesis of psoriasis through genome-wide association study (GWAS). In the present study, we investigated the putative role of A20 in epidermal keratinocytes. Immunohistochemical analysis showed that A20 was expressed in all layers of the epidermis, with an increasing pattern in the upper layers. In our model of calcium-induced keratinocyte differentiation, A20 expression was increased in a time-dependent manner. To investigate whether A20 affected keratinocyte differentiation, we overexpressed A20 in cultured keratinocytes. As a result, we noted that A20 overexpression did not affect keratinocyte differentiation, suggesting that A20 is not a direct modulator of keratinocyte differentiation. Interestingly, we found that A20 levels were decreased in psoriatic lesional skin compared to non-lesional areas. To investigate whether A20 played a role in the innate immune response of keratinocytes, we overexpressed A20 and then examined poly(I:C)-induced cytokine expression. We noted that A20 significantly inhibited poly(I:C)-induced cytokine production, and this effect was related to the inhibition of NF-κB signaling. These results suggest that the downregulation of A20 increased the susceptibility of keratinocytes to external stimuli, thus contributing to the development of psoriasis.
ISSN:1107-3756
1791-244X
DOI:10.3892/ijmm.2016.2514