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Chloroform upregulates early growth response‐1‐dependent thymic stromal lymphopoietin expression via the JNK and ERK pathways in human keratinocytes
Author(s) -
Lee Hana,
Bae Hyun Cheol,
Kim Jinhee,
Jeong Sang Hoon,
Ryu WooIn,
Son Sang Wook
Publication year - 2015
Publication title -
international journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.677
H-Index - 93
eISSN - 1365-4632
pISSN - 0011-9059
DOI - 10.1111/ijd.12946
Subject(s) - thymic stromal lymphopoietin , mapk/erk pathway , downregulation and upregulation , hacat , signal transduction , kinase , protein kinase a , keratinocyte , immunology , microbiology and biotechnology , medicine , cancer research , biology , inflammation , cell culture , biochemistry , gene , genetics
Background Exposure to volatile organic compounds ( VOC s) in the environment has been reported to exacerbate allergic inflammatory diseases, such as atopic dermatitis ( AD ). However, the exact mechanism by which VOC s induce an inflammatory response in the skin is poorly understood. Thymic stromal lymphopoietin ( TSLP ) is known to be an important factor in the initiation and maintenance of allergic inflammatory diseases, including AD . Objectives The aim of this work is to define the correlation between VOC s and TSLP . Methods The present study demonstrates dose‐dependent increases of TSLP protein and mRNA levels in keratinocytes following exposure to chloroform. We further investigated the regulatory mechanisms of chloroform‐induced TSLP expression in human keratinocytes. Results Chloroform induces early growth response‐1 (Egr‐1) protein expression in human keratinocytes. This process is mediated by the c‐ JUN N‐terminal kinase ( JNK ) and extracellular signal‐regulated kinase ( ERK ) signaling pathways. Inhibition of phosphorylated JNK and ERK significantly downregulated Egr‐1 expression, which was subsequently associated with reduced TSLP expression in chloroform‐exposed human keratinocytes. Moreover, treatment of Egr‐1 si RNA abolished chloroform‐induced TSLP protein expression and TSLP promoter transcriptional activation. Conclusions Taken together, these findings suggest that, in human keratinocytes, the upregulation of TSLP by chloroform is induced through an Egr‐1‐dependent mechanism that requires the c‐ JNK and ERK pathways. Our results suggest that exposure to chloroform may aggravate allergic skin diseases such as AD through Egr‐1‐dependent TSLP regulation.