Inhibition of Tumor Necrosis Factor-α and β Secretion by Lymphokine Activated Killer Cells by Transforming Growth Factor-β
| Autor: | Mitsuyasu Nagasaka, Atsushi Sasaki, Eiji Satoh, Shiro Isoe, Shin Nakano, Kachio Tasaka, Hirofumi Naganuma, Hideaki Nukui |
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| Rok vydání: | 1994 |
| Předmět: |
Lymphotoxin alpha
Cancer Research medicine.medical_specialty Tumor necrosis factor chemical and pharmacologic phenomena In Vitro Techniques Article Lymphokine activated killer cell Transforming Growth Factor beta Internal medicine Tumor Cells Cultured medicine Humans Secretion Killer Cells Lymphokine-Activated Lymphotoxin-alpha Lymphokine-activated killer cell biology Tumor Necrosis Factor-alpha Chemistry Lymphokine hemic and immune systems Transforming growth factor beta Molecular biology Endocrinology Oncology biology.protein Tumor necrosis factor alpha Antibody Glioblastoma Transforming growth factor Secretory Rate Immunosuppression |
| Zdroj: | Japanese Journal of Cancer Research : Gann |
| ISSN: | 0910-5050 |
| Popis: | Transforming growth factor-beta (TGF-beta) has a variety of immunosuppressive properties. We investigated the effect of TGF-beta secreted by glioblastoma (T98G) cells on the secretion of tumor necrosis factor-alpha and -beta (TNFs) by lymphokine activated killer (LAK) cells stimulated with tumor cells. The supernatant from T98G cells was preincubated with anti-TGF-beta 1 and -beta 2 neutralizing antibodies or untreated, and added to a coculture of LAK and Daudi cells. The neutralizing antibodies were added to LAK/Daudi and LAK culture, and natural human TGF-beta 1 and recombinant human TGF-beta 2 were also added to the LAK/Daudi culture. LAK cells were also cultured with T98G cells, of which the supernatant contained both active and latent forms of TGF-beta 1 and TGF-beta 2, and the neutralizing antibodies were added to the coculture. TNFs activity in the supernatants from LAK/Daudi cultures was examined by a specific bioassay. Addition of the supernatant from T98G cells to LAK/Daudi culture resulted in the inhibition of TNFs secretion by LAK cells. The inhibition was abrogated by the pretreatment of the supernatants with the anti-TGF-beta antibodies. Addition of TGF-beta 1 and TGF-beta 2 to LAK/Daudi culture inhibited TNFs secretion by LAK cells in a dose-dependent manner. Addition of anti-TGF-beta antibodies to LAK culture resulted in an increase of TNFs secretion. These results suggest that, if tumor cells have the capacity to convert TGF-beta from a latent to an active form, the active TGF-beta suppresses TNFs secretion by LAK cells stimulated with the tumor cells, and that TGF-beta secreted and activated by glioblastoma cells suppresses the propagation of immune reaction by inhibiting TNFs secretion by activated lymphocytes adjacent to tumor cells. |
| Databáze: | OpenAIRE |
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