Suppressive effects of transforming growth factor-beta1 produced by hepatocellular carcinoma cell lines on interferon-gamma production by peripheral blood mononuclear cells.
Transforming growth factor-beta1 (TGF-beta1) exerts potent immunosuppressive effects. In this study, we investigated the potential role of TGF-beta1 produced by hepatocellular carcinoma (HCC) cell lines in immunosuppression mechanisms. Using the Mv1Lu cell-growth inhibition assay and an enzyme-linked immunosorbent assay (ELISA), we detected optimal levels of TGF-beta1 in the culture supernatants conditioned by the HCC cell lines PLC/PRF/5, Hep3B, and HepG2. To determine the biological activity of TGF-beta1 in the supernatants, we examined the effects of the culture supernatants on the production of interferon (IFN)-gamma induced during the culture of peripheral blood mononuclear cells (PBMCs) stimulated with interleukin (IL)-12. IFN-gamma production of IL-12-stimulated PBMCs in the 1:1 dilution of the acid-activated conditioned medium of PLC/PRF/5, Hep3B, and HepG2 reduced to 14.7 +/- 0.8, 17.3 +/- 9.0, and 35.9 +/- 14.6%, respectively, compared with the value in the culture with control medium (complete culture medium). These results suggest that HCC cells producing TGF-beta1 may reduce the generation or activation of cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, and thus could enhance their ability to escape immune-mediated surveillance.
Mouri
Hirokazu
H
Department of Medicine and Medical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama 700 8558, Japan.
Sakaguchi
Kohsaku
K
Sawayama
Tomoyuki
T
Senoh
Tomonori
T
Ohta
Takeyuki
T
Nishimura
Mamoru
M
Fujiwara
Akiko
A
Terao
Masako
M
Shiratori
Yasushi
Y
Tsuji
Takao
T
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008113:Liver Neoplasms / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016212:Transforming Growth Factor beta / Q000502:physiology*; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D018664:Interleukin-12; D007371:Interferon-gamma