Fas ligand-induced proinflammatory transcriptional responses in reconstructed human epidermis: Recruitment of the epidermal growth factor receptor and activation of MAP kinases

Sherry M. Farley, David E. Purdy, Olga P. Ryabinina, Pascal Schneider, Bruce E. Magun, Mihail S. Iordanov

Research output: Contribution to journalArticle

26 Citations (Scopus)

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,wefound 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 thymicstromal 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.

Original languageEnglish (US)
Pages (from-to)919-928
Number of pages10
JournalJournal of Biological Chemistry
Volume283
Issue number2
DOIs
StatePublished - Jan 11 2008

Fingerprint

Fas Ligand Protein
Epidermal Growth Factor Receptor
Epidermis
Phosphotransferases
Chemical activation
Caspases
Interleukin-1
Keratinocytes
Ligands
Stevens-Johnson Syndrome
Poisons
Eczema
Cell death
Intercellular Adhesion Molecule-1
Mitogen-Activated Protein Kinases
Interleukin-8
Gene expression
Skin
Cell Death
Inflammation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Fas ligand-induced proinflammatory transcriptional responses in reconstructed human epidermis : Recruitment of the epidermal growth factor receptor and activation of MAP kinases. / Farley, Sherry M.; Purdy, David E.; Ryabinina, Olga P.; Schneider, Pascal; Magun, Bruce E.; Iordanov, Mihail S.

In: Journal of Biological Chemistry, Vol. 283, No. 2, 11.01.2008, p. 919-928.

Research output: Contribution to journalArticle

Farley, Sherry M. ; Purdy, David E. ; Ryabinina, Olga P. ; Schneider, Pascal ; Magun, Bruce E. ; Iordanov, Mihail S. / Fas ligand-induced proinflammatory transcriptional responses in reconstructed human epidermis : Recruitment of the epidermal growth factor receptor and activation of MAP kinases. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 2. pp. 919-928.
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