Fas ligand elicits a caspase-independent proinflammatory response in human keratinocytes: Implications for Dermatitis

Sherry M. Farley, Anjali D. Dotson, David E. Purdy, Aaron J. Sundholm, Pascal Schneider, Bruce E. Magun, Mihail S. Iordanov

Research output: Contribution to journalArticle

38 Citations (Scopus)

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-κB-dependent mRNA accumulation of inflammatory cytokines (tumor necrosis factor-α, IL-6, and IL-1β), chemokines (CCL2/MCP-1, CXCL1/GROα, CXCL3/GROγ, 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.

Original languageEnglish (US)
Pages (from-to)2438-2451
Number of pages14
JournalJournal of Investigative Dermatology
Volume126
Issue number11
DOIs
StatePublished - Nov 15 2006

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Dermatitis
Fas Ligand Protein
Caspases
Keratinocytes
Apoptosis
Eczema
Adhesion
Cytokines
Inflammation
Chemokine CCL5
Oligomerization
Messenger RNA
Molecules
Caspase Inhibitors
T-cells
Chemokine CCL2
Intercellular Adhesion Molecule-1
Interleukin-8
Interleukin-1
Chemokines

ASJC Scopus subject areas

  • Dermatology

Cite this

Farley, S. M., Dotson, A. D., Purdy, D. E., Sundholm, A. J., Schneider, P., Magun, B. E., & Iordanov, M. S. (2006). Fas ligand elicits a caspase-independent proinflammatory response in human keratinocytes: Implications for Dermatitis. Journal of Investigative Dermatology, 126(11), 2438-2451. https://doi.org/10.1038/sj.jid.5700477

Fas ligand elicits a caspase-independent proinflammatory response in human keratinocytes : Implications for Dermatitis. / Farley, Sherry M.; Dotson, Anjali D.; Purdy, David E.; Sundholm, Aaron J.; Schneider, Pascal; Magun, Bruce E.; Iordanov, Mihail S.

In: Journal of Investigative Dermatology, Vol. 126, No. 11, 15.11.2006, p. 2438-2451.

Research output: Contribution to journalArticle

Farley, SM, Dotson, AD, Purdy, DE, Sundholm, AJ, Schneider, P, Magun, BE & Iordanov, MS 2006, 'Fas ligand elicits a caspase-independent proinflammatory response in human keratinocytes: Implications for Dermatitis', Journal of Investigative Dermatology, vol. 126, no. 11, pp. 2438-2451. https://doi.org/10.1038/sj.jid.5700477
Farley, Sherry M. ; Dotson, Anjali D. ; Purdy, David E. ; Sundholm, Aaron J. ; Schneider, Pascal ; Magun, Bruce E. ; Iordanov, Mihail S. / Fas ligand elicits a caspase-independent proinflammatory response in human keratinocytes : Implications for Dermatitis. In: Journal of Investigative Dermatology. 2006 ; Vol. 126, No. 11. pp. 2438-2451.
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