CUP Faculty Research

Title

Fas Ligand-Induced Proinflammatory Transcriptional Responses in Reconstructed Human Epidermis

Document Type

Article

Publication Date

10-1-2007

Abstract

Fas ligand (FasL) exerts potent proapoptotic and proinflammatory actions on epidermal keratinocytes and has been implicated in the pathogenesis of eczema, toxic epidermal necrolysis, and drug-induced skin eruptions. We used reconstructed human epidermis to investigate the mechanisms of FasL-induced inflammatory responses and their relationships with FasL-triggered caspase activity. Caspase activity was a potent antagonist of the pro-inflammatory gene expression triggered by FasL prior to the onset of cell death. Furthermore, we found that FasL-stimulated autocrine production of epidermal growth factor receptor (EGFR) ligands, and the subsequent activation of EGFR and ERK1 and ERK2 mitogen-activated protein kinases, were obligatory extracellular steps for the FasL-induced expression of a subset of inflammatory mediators, including CXCL8/interleukin (IL)-8, ICAM-1, IL-1α, IL-1β, CCL20/MIP-3α, and thymic stromal lymphopoietin. These results expand the known physiological role of EGFR and its ligands from promoting keratinocyte mitogenesis and survival to mediating FasL-induced epidermal inflammation.

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Publication Information.

Farley, S. M., Purdy, D. E., Ryabinina, O. P., Schneider, P., Magun, B. E., & Iordanov, M. S. (2007). Fas ligand-induced proinflammatory transcriptional responses in reconstructed human epidermis. Recruitment of the epidermal growth factor receptor and activation of MAP kinases. The Journal of Biological Chemistry, 283(2), 919-928. doi:10.1074/jbc.M705852200

doi:10.1074/jbc.M705852200

Published In

The Journal of Biological Chemistry

Source

CU Commons -- Math and Science Department Faculty Research

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