Non-apoptotic signaling pathways activated by soluble Fas ligand in serum-starved human fibroblasts: Mitogen-activated protein kinases and NF-κB-dependent gene expression

Jin Hyung Ahn, Sun Mi Park, Ho Sung Cho, Myung Shik Lee, Jong Bok Yoon, Jan Vilcek, Tae H. Lee

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Many Fas-expressing cells do not undergo cell death upon Fas stimulation. In the normal human diploid cell line GM6112, the addition of soluble Fas ligand (sFasL) leads to morphological signs of cell death in less than 1% of cells. Treatment of serum-starved GM6112 fibroblasts with sFasL resulted in a rapid and transient phosphorylation of ERK1/2 without a significant increase in JNK and p38 activities. Unless co-treated with the protein synthesis inhibitor anisomycin, sFasL did not show gene-inducing activity in cells maintained in complete medium. However, when cells were serum-starved for 4 days, treatment with sFasL alone induced interleukin-6 gene expression and, less strongly, interleukin-8 gene expression. Sensitization of the gene-inducing activity by serum starvation correlated with NF-κB activation by sFasL. Furthermore, we found that the expression of FADD and caspase-8 was significantly reduced in serum-starved cells, whereas the level of cFLIP remained unchanged. Transfection of GM6112 cells with the antisense caspase-8 expression construct sensitized cells toward sFasL-induced NF-κB-dependent reporter activation. Our results support the notion that a change in the ratio of cFLIP and caspase-8 may be responsible for turning on the Fas-activated NF-κB pathway, which otherwise is supplanted by the death-inducing pathway.

Original languageEnglish
Pages (from-to)47100-47106
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number50
DOIs
Publication statusPublished - 2001 Dec 14

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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