title: Chloroform upregulates early growth response-1-dependent thymic stromal lymphopoietin expression via the JNK and ERK pathways in human keratinocytes.
abstract: BACKGROUND
  Exposure to volatile organic compounds (VOCs) in the environment has been reported to exacerbate allergic inflammatory diseases, such as atopic dermatitis (AD). However, the exact mechanism by which VOCs 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.
  
  
  OBJECTIVE
  The aim of this work is to define the correlation between VOCs 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 siRNA 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.
authors.affiliation: Laboratory of Cell Signaling and Nanomedicine, Department of Dermatology, Korea University College of Medicine, Seoul, South Korea.|Division of Brain, Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Hana
authors.initials: H
authors.lastname: Lee
authors.affiliation: Laboratory of Cell Signaling and Nanomedicine, Department of Dermatology, Korea University College of Medicine, Seoul, South Korea.|Division of Brain, Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Hyun Cheol
authors.initials: HC
authors.lastname: Bae
authors.affiliation: Laboratory of Cell Signaling and Nanomedicine, Department of Dermatology, Korea University College of Medicine, Seoul, South Korea.|Division of Brain, Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Jinhee
authors.initials: J
authors.lastname: Kim
authors.affiliation: Laboratory of Cell Signaling and Nanomedicine, Department of Dermatology, Korea University College of Medicine, Seoul, South Korea.|Division of Brain, Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Jeong
authors.affiliation: Laboratory of Cell Signaling and Nanomedicine, Department of Dermatology, Korea University College of Medicine, Seoul, South Korea.|Division of Brain, Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Woo-In
authors.initials: WI
authors.lastname: Ryu
authors.affiliation: Laboratory of Cell Signaling and Nanomedicine, Department of Dermatology, Korea University College of Medicine, Seoul, South Korea.|Division of Brain, Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Sang Wook
authors.initials: SW
authors.lastname: Son
mesh_terms: D002460:Cell Line; D002725:Chloroform / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D015603:Keratinocytes; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D012997:Solvents / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D055549:Volatile Organic Compounds / Q000494:pharmacology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D051766:Early Growth Response Protein 1; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012997:Solvents; D055549:Volatile Organic Compounds; D002725:Chloroform; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D000094632:Thymic Stromal Lymphopoietin