Fas Ligand Elicits a Caspase-Independent Proinflammatory Response in Human Keratinocytes: Implications for Dermatitis
| Autor: | Bruce E. Magun, Anjali D. Dotson, David E. Purdy, Mihail S. Iordanov, Pascal Schneider, Sherry M. Farley, Aaron J. Sundholm |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Keratinocytes
Fas Ligand Protein Eczema Gene Expression Apoptosis Dermatitis Dermatology Cysteine Proteinase Inhibitors Biochemistry Fas ligand Cell Line Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine medicine Humans Apoptosis/genetics Caspase Inhibitors Caspases/metabolism Cell Adhesion Molecules/genetics Cell Adhesion Molecules/metabolism 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 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 RNA Messenger Molecular Biology Caspase 030304 developmental biology 0303 health sciences biology Cell adhesion molecule NF-kappa B hemic and immune systems Cell Biology Intercellular Adhesion Molecule-1 medicine.disease medicine.anatomical_structure Caspases Protein Biosynthesis 030220 oncology & carcinogenesis Immunology Cancer research biology.protein Cytokines Eczematous dermatitis Chemokines Epidermis Keratinocyte Cell Adhesion Molecules Spongiosis |
| Zdroj: | Journal of Investigative Dermatology, vol. 126, no. 11, pp. 2438-2451 |
| ISSN: | 0022-202X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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