Irritant activation of epithelial cells is mediated via protease-dependent EGFR activation

Details

• Personal Author:
  Maffei VJ ; Newton-West M ; Swerlick RA ; White KJ
• Description:
  Although numerous studies have examined in vivo and in vitro effects of irritants, most focused on events developing hours to days after exposure. Molecular events occurring immediately after skin contact remain incompletely defined. Characterization of early events could lead to the identification of key molecular signals necessary for the production of inflammatory mediators responsible for the signs and symptoms of irritant contact dermatitis (ICD). HaCaT cells treated with sodium lauryl sulfate (SLS), a model irritant, were used to examine early molecular events of ICD. Western analysis showed SLS-mediated induction of early growth response-1 (egr-1), a transcription factor capable of regulating hallmarks of ICD such as angiogenesis, hyperproliferation, and inflammation. Additionally, de novo egr-1 expression was commensurate with transcriptional activation of egr-1 mRNA and heteronuclear RNA. Use of pharmacological inhibitors demonstrated that SLS-induced egr-1 was dependent on MEK1/p44/42 ERK, but not on p38 or JNK signaling. The EGFR inhibitor PD168393 and the metalloprotease inhibitor TAPI-2 both inhibited SLS-induced egr-1. Finally, small interfering RNA silencing of the EGFR diminished SLS-induced egr-1 mRNA. These studies suggest a role of the EGFR in SLS signaling as well as a, to our knowledge, previously unreported association between ICD and EGFR induction of egr-1. [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
• Pages in Document:
  435-442
• Volume:
  131
• Issue:
  2
• NIOSHTIC Number:
  nn:20038461
• Citation:
  J Invest Dermatol 2011 Feb; 131(2):435-442
• Contact Point Address:
  Robert A. Swerlick, Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia 30322
• Email:
  rswerli@emory.edu
• Federal Fiscal Year:
  2011
• NORA Priority Area:
  Other Occupational Concerns
• Performing Organization:
  Emory University School of Medicine, Atlanta, Georgia
• Peer Reviewed:
  True
• 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-512:42cb1fc1f9ad048e77cc81e6279271bf4544fa7231e65efa8da28367759c4d40f33e587eff37e2b0c8df577cf4c118c73961ba51d972c3c05d4be4873879490a
• Download URL:
  https://stacks.cdc.gov/view/cdc/192168/cdc_192168_DS1.pdf
• File Type:
  [PDF - 742.42 KB ]