The IL-6/sIL-6R treatment of a malignant melanoma cell line enhances susceptibility to TNF-α-induced apoptosis

Yadav Wagley, Yung Choon Yoo, Han Geuk Seo, Man Hee Rhee, Tae Hyoung Kim, Keon Wook Kang, Seung Yeol Nah, Jae Wook Oh

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Melanoma is an intractable tumor that has shown very impressive and promising response to local administration of high dose recombinant TNF-α in combination with IFN-γ in clinical studies. In this study, we investigated the effect of IL-6/sIL-6R on TNF-α-resistant B16/F10.9 melanoma cells. A low dose of TNF-α or IL-6/sIL-6R had minimal affect on the cell growth. However, the highly active fusion protein of sIL-6R and IL-6 (IL6RIL6), covalently linked by a flexible peptide, sensitized TNF-α-resistant F10.9 melanoma cells to TNF-α-induced apoptosis. Stimulation of the cells with IL6RIL6 plus TNF-α resulted in both the activation of caspase-3 and the reduction of bcl-2 expression. Flow cytometry analysis showed that IL6RIL6-upregulated TNF-R55 and TNF-R75 expression, suggesting an increase in TNF-α responsiveness by IL6RIL6 resulting from the induction of TNF receptors. Moreover, exposure of F10.9 cells to neutralizing antibody to TNF-R55 significantly inhibited IL6RIL6/TNF-α-induced cytotoxicity. These results suggest that the IL6/sIL6R/gp130 system, which sensitizes TNF-α-resistant melanoma cells to TNF-α-induced apoptosis, may provide a new target for immunotherapy.

Original languageEnglish (US)
Pages (from-to)985-991
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume354
Issue number4
DOIs
StatePublished - Mar 23 2007

Bibliographical note

Funding Information:
We thank Dr. Michel Revel (Weizmann Institute, Rehovot, Israel) for the IL6RIL6 chimera. This work was supported by research fund from Chosun University (2003).

Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.

Keywords

  • Apoptosis
  • Bcl-2
  • Caspase-3
  • IL-6
  • TNF-R55
  • TNF-α
  • sIL-6R

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