DOWN-REGULATION OF MURINE FIBROSARCOMA TRANSFORMING GROWTH-FACTOR-BETA-1 EXPRESSION BY INTERLEUKIN-7
DOWN-REGULATION OF MURINE FIBROSARCOMA TRANSFORMING GROWTH-FACTOR-BETA-1 EXPRESSION BY INTERLEUKIN-7
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DOI：
10.1093/jnci/87.8.593
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发表时间：
1995-04-19
影响因子：
10.3
通讯作者：
MCBRIDE, WH
中科院分区：
文献类型：
--
作者：
DUBINETT, SM;HUANG, M;MCBRIDE, WH
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
