Interleukin-2 (IL-2) Augments the Expression of Transforming Growth Factor Beta in Patients with Disseminated Cancer

1993 ◽  
pp. 425-433 ◽  
Author(s):  
Pauli Puolakkainen ◽  
Paolo Alberto Paciucci ◽  
Jane E. Ranchalis ◽  
Leslie Oleksowicz ◽  
Daniel R. Twardzik
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Interleukin 2 ◽  
Growth Factor Beta

scholarly journals Identification of transforming growth factor-beta as a contaminant in factor VIII concentrates: a possible link with immunosuppressive effects in hemophiliacs

Blood ◽  
1994 ◽  
Vol 84 (6) ◽  
pp. 2021-2030
Author(s):  
M Wadhwa ◽  
P Dilger ◽  
J Tubbs ◽  
A Mire-Sluis ◽  
T Barrowcliffe ◽  
...  
Keyword(s):  
T Cells ◽  
Growth Factor ◽  
Factor Viii ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Interleukin 2 ◽  
Contributory Factor ◽  
Tgf Beta ◽  
Factor Viii Concentrates ◽  
Growth Factor Beta

In previous studies, we have shown that some, but not all low-, intermediate-, and high-purity factor VIII concentrates inhibit interleukin-2 (IL-2) secretion from phytohemagglutinin (PHA)-stimulated T lymphocytes. We now present evidence that this inhibitory action of concentrates is, at least in part, due to contamination with transforming growth factor-beta (TGF-beta). Originally identified in platelets, TGF-beta is a 25-kD homodimer that has been shown to be a natural and potent inhibitor of many immunologic responses. Using a specific bioassay, we have measured TGF-beta in various factor VIII concentrates. While some concentrates contained substantial amounts of the cytokine, there was a wide variation in concentrations of TGF-beta in different products. These levels correlated with the degree of inhibition of IL-2 secretion from T cells exhibited by each product (P = .0001). Noninhibitory concentrates contained no detectable TGF-beta. Addition of a specific TGF-beta 1 antibody reversed the inhibitory effect of some concentrates on IL-2 secretion by PHA-stimulated Jurkat T cells and interleukin-5 (IL-5)-induced proliferation of an erythroleukemic cell line. These findings suggest that TGF-beta contamination is a major contributory factor to the inhibitory activity of some factor VIII concentrates on cytokine secretion or activity, and may partially explain the reported immunosuppressive effects in recipients of these blood products.

scholarly journals Inhibition of Nb2 T-lymphoma cell growth by transforming growth factor-β

1988 ◽  
Vol 253 (1) ◽  
pp. 295-298 ◽  
Author(s):  
E J Rayhel ◽  
D A Prentice ◽  
P S Tabor ◽  
W H Flurkey ◽  
R W Geib ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Interleukin 2 ◽  
Transforming Growth Factor Β ◽  
Tgf Beta ◽  
Inhibitory Effects ◽  
Nb2 Cells ◽  
Growth Factor Beta ◽  
T Lymphoma

Transforming growth factor-beta (TGF-beta) inhibits proliferation of Nb2 cells, a rat T lymphoma, in response to lactogens and interleukin-2. Prostaglandins may play an important role in the pathway through which TGF-beta exerts its inhibitory actions, because prostaglandin E2 also inhibits proliferation of Nb2 cells, and indomethacin, an inhibitor of prostaglandin synthesis, reverses the inhibitory effects of TGF-beta on Nb2 cell proliferation.

scholarly journals The gamma subunit of the interleukin-2 receptor is expressed in human monocytes and modulated by interleukin-2, interferon gamma, and transforming growth factor beta 1

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3462-3467 ◽  
Author(s):  
MC Bosco ◽  
I Espinoza-Delgado ◽  
M Schwabe ◽  
SM Russell ◽  
WJ Leonard ◽  
...  
Keyword(s):  
Growth Factor ◽  
Interferon Gamma ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Interleukin 2 ◽  
Human Monocytes ◽  
Gamma Chain ◽  
Ifn Gamma ◽  
Gamma Subunit ◽  
Growth Factor Beta

Abstract The interleukin-2 receptor gamma (IL-2R gamma) chain is a newly recognized component of the IL-2R of lymphoid cells that is required for their response to IL-2. We investigated the expression of IL-2R gamma protein in human monocytes by Western blot analysis using an antiserum specific for IL-2R gamma. We found that IL-2R gamma subunit is constitutively expressed in human monocytes and upregulated by the monocyte-activating factors IL-2 and interferon gamma (IFN gamma). Furthermore, we show that transforming growth factor beta 1 (TGF beta 1) downmodulates, in a dose-dependent manner, basal and IL-2-induced, but not IFN gamma-induced, IL-2R gamma chain expression, and this effect may be responsible for TGF beta 1 suppressive activity on IL-2- activated monocytes. Overall, these results show that the expression of the IL-2R gamma subunit in human monocytes is tightly regulated by the cytokine network, suggesting a critical role played by this protein on monocyte activation.

scholarly journals Transforming growth factor beta and cyclosporin A inhibit the inducible activity of the interleukin-2 gene in T cells through a noncanonical octamer-binding site.

1993 ◽  
Vol 13 (2) ◽  
pp. 1155-1162 ◽  
Author(s):  
T Brabletz ◽  
I Pfeuffer ◽  
E Schorr ◽  
F Siebelt ◽  
T Wirth ◽  
...  
Keyword(s):  
Growth Factor ◽  
T Lymphocytes ◽  
Cyclosporin A ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Interleukin 2 ◽  
Tgf Beta ◽  
Enhancer Activity ◽  
Upstream Promoter ◽  
Growth Factor Beta

Transforming growth factor beta (TGF-beta) has a growth-inhibitory effect on numerous different cell types of the immune system, including T lymphocytes. We show in this study that the inhibitory action of TGF-beta on T lymphocytes is accompanied by a block of interleukin 2 (IL-2) gene expression which is mediated, at least in part, by inhibition of IL-2 promoter/enhancer activity. The functional analysis of cis-regulatory (proto-enhancer) elements of the IL-2 enhancer/promoter region showed that the most TGF-beta-responsive element maps to its so-called upstream promoter site. The proto-enhancer activity of the upstream promoter site element is also inhibited by cyclosporin A. The upstream promoter site DNA harbors two noncanonical, closely linked binding sequences for octamer and AP-1-like factors. Both sites are involved in the establishment of IL-2 enhancer activity. Since the activity of genuine octamer sites but not that of AP-1-binding sites is also impaired by TGF-beta and cyclosporin A in El4 T lymphoma cells, we conclude that both immunosuppressives interfere with the activity but not the DNA binding of octamer factors in T lymphocytes.

scholarly journals The gamma subunit of the interleukin-2 receptor is expressed in human monocytes and modulated by interleukin-2, interferon gamma, and transforming growth factor beta 1

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3462-3467 ◽  
Author(s):  
MC Bosco ◽  
I Espinoza-Delgado ◽  
M Schwabe ◽  
SM Russell ◽  
WJ Leonard ◽  
...  
Keyword(s):  
Growth Factor ◽  
Interferon Gamma ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Interleukin 2 ◽  
Human Monocytes ◽  
Gamma Chain ◽  
Ifn Gamma ◽  
Gamma Subunit ◽  
Growth Factor Beta

The interleukin-2 receptor gamma (IL-2R gamma) chain is a newly recognized component of the IL-2R of lymphoid cells that is required for their response to IL-2. We investigated the expression of IL-2R gamma protein in human monocytes by Western blot analysis using an antiserum specific for IL-2R gamma. We found that IL-2R gamma subunit is constitutively expressed in human monocytes and upregulated by the monocyte-activating factors IL-2 and interferon gamma (IFN gamma). Furthermore, we show that transforming growth factor beta 1 (TGF beta 1) downmodulates, in a dose-dependent manner, basal and IL-2-induced, but not IFN gamma-induced, IL-2R gamma chain expression, and this effect may be responsible for TGF beta 1 suppressive activity on IL-2- activated monocytes. Overall, these results show that the expression of the IL-2R gamma subunit in human monocytes is tightly regulated by the cytokine network, suggesting a critical role played by this protein on monocyte activation.

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