Fas ligand elicits a caspase-independent proinflammatory response in human keratinocytes: implications for dermatitis.

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Serval ID
serval:BIB_5911D04EE042
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Fas ligand elicits a caspase-independent proinflammatory response in human keratinocytes: implications for dermatitis.
Journal
Journal of Investigative Dermatology
Author(s)
Farley S.M., Dotson A.D., Purdy D.E., Sundholm A.J., Schneider P., Magun B.E., Iordanov M.S.
ISSN
1523-1747 (Electronic)
ISSN-L
0022-202X
Publication state
Published
Issued date
2006
Peer-reviewed
Oui
Volume
126
Number
11
Pages
2438-2451
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Fas ligand (FasL) causes apoptosis of epidermal keratinocytes and triggers the appearance of spongiosis in eczematous dermatitis. We demonstrate here that FasL also aggravates inflammation by triggering the expression of proinflammatory cytokines, chemokines, and adhesion molecules in keratinocytes. In HaCaT cells and in reconstructed human epidermis (RHE), FasL triggered a NF-kappaB-dependent mRNA accumulation of inflammatory cytokines (tumor necrosis factor-alpha, IL-6, and IL-1beta), chemokines (CCL2/MCP-1, CXCL1/GROalpha, CXCL3/GROgamma, and CXCL8/IL-8), and the adhesion molecule ICAM-1. Oligomerization of Fas was required both for apoptosis and for gene expression. Inhibition of caspase activity abolished FasL-dependent apoptosis; however, it failed to suppress the expression of FasL-induced genes. Additionally, in the presence of caspase inhibitors, but not in their absence, FasL triggered the accumulation of CCL5/RANTES (regulated on activation normal T cell expressed and secreted) mRNA. Our findings identify a novel proinflammatory role of FasL in keratinocytes that is independent of caspase activity and is separable from apoptosis. Thus, in addition to causing spongiosis, FasL may play a direct role in triggering and/or sustaining inflammation in eczemas.
Keywords
Apoptosis/genetics, Caspase Inhibitors, Caspases/metabolism, Cell Adhesion Molecules/genetics, Cell Adhesion Molecules/metabolism, Cell Line, Chemokines/genetics, Chemokines/metabolism, Cysteine Proteinase Inhibitors/pharmacology, Cytokines/genetics, Cytokines/metabolism, Dermatitis/etiology, Dermatitis/genetics, Eczema/etiology, Eczema/genetics, Epidermis/drug effects, Epidermis/metabolism, Fas Ligand Protein/pharmacology, Fas Ligand Protein/physiology, Gene Expression/drug effects, Gene Expression Regulation, Humans, Intercellular Adhesion Molecule-1/genetics, Intercellular Adhesion Molecule-1/metabolism, Keratinocytes/chemistry, Keratinocytes/drug effects, NF-kappa B/antagonists & inhibitors, NF-kappa B/genetics, Protein Biosynthesis/genetics, RNA, Messenger/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
19/01/2008 17:30
Last modification date
20/08/2019 14:12
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