Fas ligand-induced proinflammatory transcriptional responses in reconstructed human epidermis. Recruitment of the epidermal growth factor receptor and activation of MAP kinases.
J Biol Chem
; 283(2): 919-28, 2008 Jan 11.
Article
in En
| MEDLINE
| ID: mdl-17977827
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-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.
Search on Google
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription, Genetic
/
Keratinocytes
/
Epidermis
/
Fas Ligand Protein
/
ErbB Receptors
/
Inflammation
Limits:
Humans
/
Newborn
Language:
En
Journal:
J Biol Chem
Year:
2008
Document type:
Article
Affiliation country:
Estados Unidos