Sodium Lauryl Sulfate Induces VEGF Expression in Immortalized Keratinocytes via an Egr-1, MEK1-Dependent Mechanism

Details

• Personal Author:
  Casper KA ; Newton-West M ; O'Reilly FM ; Swerlick RA
• Description:
  Irritant contact dermatitis (ICD) is characterized acutely by erythema and edema evolving with chronic exposure to hyperkeratosis and lichenification. The cellular and molecular mechanisms involved in ICD are poorly understood. Keratinocytes are a major target for irritants resulting in activation and secretion of soluble mediators e.g vascular endothelial growth factor (VEGF), a powerful pro-inflammatory and angiogenic agent. We determined whether sodium lauryl sulfate (SLS), a model irritant, induces VEGF expression in HaCat cells at non-toxic concentrations. In order to best define the appropriate dosing for maximum cell viability, testing with SLS was performed at different concentrations (0.1-0.001%) and exposure times (5-60 minutes). Five minute exposure to concentrations of SLS as high as 0.01% resulted in minimal effects on cell viability. Under these conditions, VEGF mRNA expression was upregulated 5-30 fold after one hour, responses that were comparable to TGFa treatment. Using oligonucleotide probes from the egr-1 responsive region of the VEGF promoter in EMSA, we demonstrated that SLS treatment resulted in the appearance of nuclear complexes that bound the VEGF promoter derived EMSA probe. Supershift analysis demonstrated these complexes contained egr-1 protein. SLS treatment resulted in increased levels of steady state egr-1 mRNA, suggesting that SLS may target egr-1 gene expression. As previous studies have linked egr-1 induction to MEK1 activation, we examined whether PD98059, a specific inhibitor of MEK1, blocked SLS-induced VEGF expression. Pretreatment of HaCat cells with PD98059 prior to SLS treatment blocked VEGF induction as well as SLS mediated egr-1 expression, whereas the proteasomal inhibitor MG-132 had no effect. These data suggest that irritants such as SLS may target MEK1 activation and egr-1 induction. These studies provide insight into novel approaches for the development of relevant in vitro test systems to investigate the mechanisms and prevention of ICD. [Description provided by NIOSH]
• Subjects:
  Dermatitis Energy Metabolism Irritants Occupational Health Safety Skin
• Keywords:
  Contact-dermatitis Drug-interaction Humans Metabolism Pharmacology Skin-exposure Skin-irritants Skin-sensitivity
• ISSN:
  0022-202X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Georgia ; OSHA Region 4
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  121
• Issue:
  1
• NIOSHTIC Number:
  nn:20058816
• Citation:
  J Invest Dermatol 2003 Jul; 121(1):0022
• Contact Point Address:
  Robert A. Swerlick, Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia 30322
• Email:
  rswerli@emory.edu
• Federal Fiscal Year:
  2003
• NORA Priority Area:
  Other Occupational Concerns
• Performing Organization:
  Emory University School of Medicine, Atlanta, Georgia
• Peer Reviewed:
  False
• Start Date:
  20000930
• Source Full Name:
  Journal of Investigative Dermatology
• End Date:
  20020929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:be3ccd9dd2aae39a1a9b43ad852a2e026532cb7e162b5a5dcc76a5aad0dcd264fd570c5c548006fcb0b8eab8ad4750d4ed46c8b074c2be254857f3d95fff1a91
• Download URL:
  https://stacks.cdc.gov/view/cdc/223209/cdc_223209_DS1.pdf
• File Type:
  [PDF - 2.32 MB ]