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Down-regulation of murine fibrosarcoma transforming growth factor-beta-1 expression by interleukin 7
- Source :
- Journal of the National Cancer Institute. April 19, 1995, Vol. 87 Issue 8, p593, 5 p.
- Publication Year :
- 1995
-
Abstract
- Background. Cytokine genes encode proteins that modulate immune system responses. Modification of tumor cells by the introduction of cytokine genes has been used as a strategy to augment host immunity. Interleukin 7 (IL-7) gene transfer enhances the immune response to tumor cells and can result in tumor regression. Transforming growth factor-[beta]1 TGF-[beta]1) is a potent immunosuppressive cytokine produced by many tumors. We have previously reported that recombinant IL-7 decreases the expression of TGF-[beta]1 by murine macrophages. Purpose: This study investigates the inhibition of tumor-derived TGF-[beta]1 production as a possible mechanism for the enhanced antitumor immunity that accompanies IL-7 gene transfer. Methods: A fibrosarcoma cell line (FSA-JmIL-7) genetically modified to produce IL-7 was used to evaluate the effects of IL-7 on tumor production of TGF-[beta]1. The control cell line (FSA-Jneo) originated from the same parental fibrosarcoma cell line (FSA) and was produced by transduction with the same retroviral vector without the IL-7 gene. Fsa-Jneo and FSA-JmIL-7 tumor cells were evaluated for the expression of TGF-[beta]1 messenger RNA (mRNA). To determine if the observed change in TGF-[beta]1 MRNA was associated with an alteration in protein secretion, we compared supernatants from tumor cell cultures for TGF-[beta]1 production. Specific anti-TGF-[beta]1 monoclonal antibody (MAb) was used to confirm the role of TGF-[beta]1 in these assays. Results: Compared with FSA parental and FSA-Jneo cells, FSA-JmIL-7 cells expressed TGF-[beta]1 mRNA at a lower level. Compared with supernatants from FSA-Jneo cells, FSA-JmIL-7 supernatants contained consistently lower levels of TGF-[beta]1 activity (P
Details
- ISSN :
- 00278874
- Volume :
- 87
- Issue :
- 8
- Database :
- Gale General OneFile
- Journal :
- Journal of the National Cancer Institute
- Publication Type :
- Periodical
- Accession number :
- edsgcl.16898976