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PMID: 7961125 Published · ppublish English Journal Article

Inhibition of tumor necrosis factor-alpha and -beta secretion by lymphokine activated killer cells by transforming growth factor-beta.

Japanese journal of cancer research : Gann ·Vol. 85 ·No. 9 ·1994-09-00 ·Pages 952-7

Naganuma H, Sasaki A, Satoh E, Nagasaka M, Nakano S, Isoe S, Tasaka K, Nukui H

Abstract

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.

MeSH Terms
Glioblastoma/metabolism Humans In Vitro Techniques Killer Cells, Lymphokine-Activated/physiology Lymphotoxin-alpha/metabolism Secretory Rate Transforming Growth Factor beta/physiology Tumor Cells, Cultured Tumor Necrosis Factor-alpha/metabolism
Chemicals
Lymphotoxin-alpha Transforming Growth Factor beta Tumor Necrosis Factor-alpha
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Naganuma H
Department of Neurosurgery, Yamanashi Medical University.
Sasaki A
Satoh E
Nagasaka M
Nakano S
Isoe S
Tasaka K
Nukui H
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Article Info
Journal
Japanese journal of cancer research : Gann
Abbr.
Jpn J Cancer Res
ISSN
0910-5050
DOI
10.1111/j.1349-7006.1994.tb02974.x
Published
1994-09-00
Pages
952-7
Language
English
Region
Japan
NLM ID
8509412
PMCID
PMC5919594
Subset
IM
External Links
PubMed source DOI: 10.1111/j.1349-7006.1994.tb02974.x PMC Full Text
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