The IL-6/sIL-6R treatment of a malignant melanoma cell line enhances susceptibility to TNF-{alpha}-induced apoptosis
- Department of Anatomy, College of Medicine, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju 501-759 (Korea, Republic of)
- Department of Microbiology, College of Medicine, Konyang University, Daejeon 302-718 (Korea, Republic of)
- Department of Pharmacology, Gyeongsang Institute of Health Science, College of Medicine, Gyeongsang National University, Jinju 660-751 (Korea, Republic of)
- College of Veterinary Medicine, Kyungpook National University, Daegu 702-701 (Korea, Republic of)
- Department of Biochemistry and Molecular Biology, College of Medicine, Chosun University, Gwangju 501-759 (Korea, Republic of)
- College of Pharmacy, Chosun University, Gwangju 501-759 (Korea, Republic of)
- Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 143-701 (Korea, Republic of)
Melanoma is an intractable tumor that has shown very impressive and promising response to local administration of high dose recombinant TNF-{alpha} in combination with IFN-{gamma} in clinical studies. In this study, we investigated the effect of IL-6/sIL-6R on TNF-{alpha}-resistant B16/F10.9 melanoma cells. A low dose of TNF-{alpha} 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-{alpha}-resistant F10.9 melanoma cells to TNF-{alpha}-induced apoptosis. Stimulation of the cells with IL6RIL6 plus TNF-{alpha} 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-{alpha} 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-{alpha}-induced cytotoxicity. These results suggest that the IL6/sIL6R/gp130 system, which sensitizes TNF-{alpha}-resistant melanoma cells to TNF-{alpha}-induced apoptosis, may provide a new target for immunotherapy.
- OSTI ID:
- 20979845
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 354, Issue 4; Other Information: DOI: 10.1016/j.bbrc.2007.01.083; PII: S0006-291X(07)00125-8; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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