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

Authors
White-KJ; Maffei-VJ; Newton-West-M; Swerlick-RA
Source
J Invest Dermatol 2011 Feb; 131(2):435-442
NIOSHTIC No.
20038461
Abstract
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.
Keywords
Contact-dermatitis; Dermatitis; Irritants; Humans; Pharmacology; Drug-interaction; Skin; Skin-exposure; Skin-irritants; Skin-sensitivity; Metabolism
Contact
Robert A. Swerlick, Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia 30322
CODEN
JIDEAE
Publication Date
20110201
Document Type
Journal Article
Email Address
rswerli@emory.edu
Funding Amount
228750
Funding Type
Grant
Fiscal Year
2011
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R21-OH-007340
Issue of Publication
2
ISSN
0022-202X
Priority Area
Other Occupational Concerns
Source Name
Journal of Investigative Dermatology
State
GA
Performing Organization
Emory University School of Medicine, Atlanta, Georgia
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