Activation of skin cells and transcription factors by skin irritants.
Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, R21-OH-007340, 2002 Dec; :1-14
Irritant dermatitis is a source of significant workplace injury and morbidity. Our understanding of how irritants interact with the skin is minimal and expansion of our knowledge base regarding mechanisms mediating irritant action will provide us with a rationale basis of new approaches to prevention and treatment. The hypothesis proposed In this exploratory grant was that irritants affect the function or expression of transcription factors linked to the activity of pro-inflammatory genes. Activation or induced expression of pro-inflammatory genes by irritants results in the clinical manifestations of inflammation in the tissues exposed to irritants. The studies done in the proposal demonstrated that a common model detergent irritant, sodium lauryl sulfate, induces the expression of vascular endothelial growth factor (vascular permeability factor; VEGF/VPF) in a keratinocytes cell line in vitro. This induction appears to be mediated via induction of early growth factor 1 (egr-1), a transcription factor linked to cellular stress and injury. The induction of egr-l was mediated via activation of the MAP kinase MEK1, as evidenced by inhibition of both egr-1 and VEGF induction by the specific MEK1 inhibitor PD98059. These data are the first description of a molecular mechanism linking the edematous and erythematous response to detergent exposure to induction of agents which induce increases in vascular permeability and other elements of the inflammatory response. These data provide a rational framework for the development of large scale in vitro screening assays to assess irritancy of compounds. They also provide novel approaches for the prevention and treatment of irritant dermatitis.
Skin-irritants; Dermatitis; Work-environment; Injuries; Morbidity-rates; Irritants; In-vitro-studies; Sodium-compounds
Department of Dermatology, Emory University School of Medicine, WMB 5014, 1639 Pierce Drive, Atlanta, GA 30322
Final Grant Report
Other Occupational Concerns
National Institute for Occupational Safety and Health
Emory University School of Medicine, Atlanta, Georgia