Up-regulation of TNF-alpha secretion by cigarette smoke is mediated by Egr-1 in HaCaT human keratinocytes

Sang Hoon Jeong, Jae Hong Park, Ji Na Kim, Yoon Hee Park, Soon Young Shin, Young Han Lee, Young Chul Kye, Sang Wook Son

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61 Citations (Scopus)


Many epidemiologic studies have pointed to a significant association between cigarette smoking and inflammatory skin disease such as psoriasis. Cigarette smoke induces expression of regulators of inflammation such as interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor (TNF)-α. It was recently demonstrated that early growth response-1 (Egr-1) transcription factor is significantly up-regulated in the skin lesions of patients with psoriasis. The mechanism by which cigarette smoke extract (CSE) regulates inflammatory cytokine expression in keratinocyte was still unknown. The aim of this study was to investigate the signalling of CSE-induced Egr-1 expression and the role for Egr-1 in CSE-induced TNF-α expression. Cytotoxicity of CSE in HaCaT cells was measured by thiazolyl blue tetrazolium bromide (MTT) assay. CSE-induced Egr-1 expression was investigated by western blot, luciferase reporter assay and confocal microscopy. TNF-α expression was measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Involvement of Egr-1 in CSE-induced TNF-α secretion was determined by using Egr-1 specific siRNA. CSE increases the Egr-1 expression, promoter activity and its nuclear translocation in human HaCaT keratinocytes. CSE activates mitogen-activated protein kinase (MAPK) pathways including extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). Up-regulation of Egr-1 expression by CSE stimulation was found to be inhibited by an ERK and JNK but not p38 inhibitor. CSE increases TNF-α expression and secretion. This increase is mediated by CSE-induced Egr-1 expression. Our results showed that CSE induces Egr-1 expression via MAPK pathway in human keratinocytes and TNF-α expression by Egr-1. This pathway may contribute to the development of inflammatory disease such as psoriasis.

Original languageEnglish
Pages (from-to)e206-e212
JournalExperimental Dermatology
Issue number8
Publication statusPublished - 2010 Aug
Externally publishedYes


  • Cigarette smoke
  • Egr-1
  • Psoriasis
  • TNF alpha

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology


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