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

Citation data:

The Journal of biological chemistry, ISSN: 0021-9258, Vol: 283, Issue: 2, Page: 919-28

Publication Year:
2008
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Citations 26
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Repository URL:
http://commons.cu-portland.edu/msfacultyresearch/26; https://ohsu.pure.elsevier.com/en/publications/679a5968-4106-4519-9921-50b09c913284
PMID:
17977827
DOI:
10.1074/jbc.m705852200
Author(s):
Farley, Sherry M.; Purdy, David E.; Ryabinina, Olga P.; Schneider, Pascal; Magun, Bruce E.; Iordanov, Mihail S.
Publisher(s):
American Society for Biochemistry & Molecular Biology (ASBMB)
Tags:
Biochemistry, Genetics and Molecular Biology; Biochemistry; Microbiology
article description
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-1alpha, IL-1beta, CCL20/MIP-3alpha, 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.