HIV-Nef enhances interleukin-2 production and phosphatidylinositol 3-kinase activity in a human T cell line

AIDS ◽  
2000 ◽  
Vol 14 (12) ◽  
pp. 1701-1707 ◽  
Author(s):  
Stephen D. Schibeci ◽  
Alison O. Clegg ◽  
Robyn A. Biti ◽  
Kimitaka Sagawa ◽  
Graeme J. Stewart ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Line ◽  
Kinase Activity ◽  
Interleukin 2 ◽  
Phosphatidylinositol 3 Kinase ◽  
Human T Cell ◽  
Human T Cell Line ◽  
Phosphatidylinositol 3

A yeast-based screening system identified bakkenolide B contained in Petasites japonicus as an inhibitor of interleukin-2 production in a human T cell line

2021 ◽  
Author(s):  
Shota Uesugi ◽  
Mayuka Hakozaki ◽  
Yuko Kanno ◽  
Honoka Takahashi ◽  
Yui Kudo ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Line ◽  
Screening Method ◽  
Interleukin 2 ◽  
Jurkat Cells ◽  
Yeast Cells ◽  
Wild Plant ◽  
Human T Cell ◽  
Petasites Japonicus ◽  
Human T Cell Line

Abstract Ca2+ signaling is related to various diseases such as allergies, diabetes, and cancer. We explored Ca2+ signaling inhibitors in natural resources using a yeast-based screening method, and found bakkenolide B from the flower buds of edible wild plant, Petasites japonicus, using the YNS17 strain (zds1Δ erg3Δ pdr1/3Δ). Bakkenolide B exhibited growth-restoring activity against the YNS17 strain and induced Li+ sensitivity of wild-type yeast cells, suggesting that it inhibits the calcineurin pathway. Additionally, bakkenolide B inhibited interleukin-2 production at gene and protein levels in Jurkat cells, a human T cell line, but not the in vitro phosphatase activity of human recombinant calcineurin, an upstream regulator of interleukin-2 production. Furthermore, bakkenolide A showed weak activity in YNS17 and Jurkat cells compared with bakkenolide B. These findings revealed new biological effects and the structure-activity relationships of bakkenolides contained in Petasites japonicus as inhibitors of interleukin-2 production in human T cells.

Kinetics of interleukin 2 mRNA and protein produced in the human T-cell line Jurkat and the effect of cyclosporin A

Biochemistry ◽  
1989 ◽  
Vol 28 (4) ◽  
pp. 1791-1797 ◽  
Author(s):  
Rene Nordmann ◽  
Elsebeth Andersen ◽  
Rene Trussardi ◽  
Norman A. Mazer
Keyword(s):  
T Cell ◽  
Cyclosporin A ◽  
Cell Line ◽  
Interleukin 2 ◽  
Human T Cell ◽  
Kinetics Of ◽  
Human T Cell Line

scholarly journals Autocrine growth of a human T-cell line is inhibited by cyclosporin A

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 588-592 ◽  
Author(s):  
A Dautry-Varsat ◽  
A Hemar ◽  
V Cornet ◽  
V Duprez
Keyword(s):  
T Cell ◽  
Cyclosporin A ◽  
Cell Line ◽  
Tumor Cells ◽  
Interleukin 2 ◽  
Growth Stimulation ◽  
Immunosuppressive Agent ◽  
Autocrine Growth ◽  
Human T Cell ◽  
Human T Cell Line

Abstract The effect of cyclosporin A (CsA), a potent immunosuppressive agent, on a human T-cell line, IARC 301, which constitutively secretes interleukin-2 (IL-2) and expresses high-affinity IL-2 receptors, was investigated. We show that CsA inhibits IARC 301 cell growth. CsA also prevents the constitutive secretion of IL-2 in this T-cell line by blocking transcription of the IL-2 gene. If exogenous IL-2 is added together with CsA for 3 days, the cells grow as well as untreated controls. Thus, under such conditions, CsA inhibits IARC 301 growth by preventing its endogenous constitutive IL-2 synthesis. This demonstrates that IL-2 stimulates the proliferation of this cell line by an autocrine pathway, in agreement with our previous data. We also show for the first time, that CsA not only can inhibit IL-2 production of T cells upon activation, but that it can also prevent ongoing constitutive IL-2 synthesis of a T-cell line. Autocrine growth stimulation of tumor cells by cytokines has been demonstrated in a few cases. CsA inhibits synthesis of several cytokines. Probing for the autocrine growth of tumor cells by studying the effect of CsA and its reversibility by cytokines on their proliferation may be simple and useful.

scholarly journals Establishment of an interleukin 2-dependent human T cell line from a patient with T cell chronic lymphocytic leukemia who is not infected with human T cell leukemia/lymphoma virus

Blood ◽  
1987 ◽  
Vol 70 (4) ◽  
pp. 1069-1072 ◽  
Author(s):  
T Hori ◽  
T Uchiyama ◽  
M Tsudo ◽  
H Umadome ◽  
H Ohno ◽  
...  
Keyword(s):  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Cell Line ◽  
Interleukin 2 ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Cell Leukemia ◽  
Human T Cell ◽  
Human T Cell Line ◽  
Cell Chronic Lymphocytic Leukemia

We established an interleukin 2 (IL-2)-dependent human T cell line, Kit 225, from a patient with T cell chronic lymphocytic leukemia (T-CLL) with OKT3+, -T4+, -T8- phenotype. Southern blot analysis showed that Kit 225 is not infected with human T cell leukemia/lymphoma virus (HTLV) type I or II, and is probably derived from the major clone in the fresh leukemic cells. Kit 225 cells express a large amount of IL 2 receptors constitutively and their growth is absolutely dependent on IL 2. No other stimuli, such as lectins or antigens, are required for maintaining the responsiveness to IL 2. As abnormal IL 2 receptor expression was also seen originally in the fresh leukemic cells, the establishment of this cell line with IL 2 suggests that IL 2-mediated T cell proliferation is involved in the leukemogenesis of some cases of HTLV-negative T-CLL.

Dispensability of Jak1 tyrosine kinase for interleukin-2-induced cell growth signaling in a human T cell line

1996 ◽  
Vol 26 (6) ◽  
pp. 1322-1327 ◽  
Author(s):  
Masaya Higuchi ◽  
Hironobu Asao ◽  
Nobuyuki Tanaka ◽  
Katsuhiko Oda ◽  
Toshikazu Takeshita ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Growth ◽  
Tyrosine Kinase ◽  
Cell Line ◽  
Interleukin 2 ◽  
Human T Cell ◽  
Human T Cell Line

scholarly journals Autocrine growth of a human T-cell line is inhibited by cyclosporin A

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 588-592
Author(s):  
A Dautry-Varsat ◽  
A Hemar ◽  
V Cornet ◽  
V Duprez
Keyword(s):  
T Cell ◽  
Cyclosporin A ◽  
Cell Line ◽  
Tumor Cells ◽  
Interleukin 2 ◽  
Growth Stimulation ◽  
Immunosuppressive Agent ◽  
Autocrine Growth ◽  
Human T Cell ◽  
Human T Cell Line

The effect of cyclosporin A (CsA), a potent immunosuppressive agent, on a human T-cell line, IARC 301, which constitutively secretes interleukin-2 (IL-2) and expresses high-affinity IL-2 receptors, was investigated. We show that CsA inhibits IARC 301 cell growth. CsA also prevents the constitutive secretion of IL-2 in this T-cell line by blocking transcription of the IL-2 gene. If exogenous IL-2 is added together with CsA for 3 days, the cells grow as well as untreated controls. Thus, under such conditions, CsA inhibits IARC 301 growth by preventing its endogenous constitutive IL-2 synthesis. This demonstrates that IL-2 stimulates the proliferation of this cell line by an autocrine pathway, in agreement with our previous data. We also show for the first time, that CsA not only can inhibit IL-2 production of T cells upon activation, but that it can also prevent ongoing constitutive IL-2 synthesis of a T-cell line. Autocrine growth stimulation of tumor cells by cytokines has been demonstrated in a few cases. CsA inhibits synthesis of several cytokines. Probing for the autocrine growth of tumor cells by studying the effect of CsA and its reversibility by cytokines on their proliferation may be simple and useful.

scholarly journals The Src-family kinase, Fyn, regulates the activation of phosphatidylinositol 3-kinase in an interleukin 2-responsive T cell line.

1994 ◽  
Vol 179 (6) ◽  
pp. 1799-1808 ◽  
Author(s):  
L M Karnitz ◽  
S L Sutor ◽  
R T Abraham
Keyword(s):  
T Cells ◽  
T Cell ◽  
Growth Factor ◽  
Cell Line ◽  
Tyrosine Phosphorylation ◽  
Interleukin 2 ◽  
Pi3 Kinase ◽  
Src Family Kinase ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3

The proliferation of antigen-activated T cells is mediated by the T cell-derived growth factor, interleukin 2 (IL-2). The biochemical signaling cascades initiating IL-2-induced growth are dependent upon protein tyrosine kinase (PTK) activity. One IL-2-regulated PTK implicated in this cascade is the Src-family kinase, Fyn. Previous studies have described a physical association between Fyn and a potential downstream substrate, phosphatidylinositol 3-kinase (PI3-kinase) as well as the IL-2-dependent activation of PI3-kinase in T cells; however, the role of Fyn in IL-2-induced PI3-kinase activation remains unclear. In this report, we demonstrate that IL-2 stimulation triggers tyrosine phosphorylation of the p85 subunit of PI3-kinase in the murine T cell line, CTLL-2. Lysates prepared from growth factor-deprived and IL-2-stimulated T cells reconstituted both the binding of CTLL-2 cell-derived Fyn to and the IL-2-inducible tyrosine phosphorylation of exogenously added recombinant p85. Furthermore, overexpression of wild-type Fyn in these cells enhanced both the basal and IL-2-mediated activation of PI3-kinase. Additional studies of the Fyn-PI3-kinase interaction demonstrated that the Src homology 3 (SH3) domain of Fyn constitutes a direct binding site for the p85 subunit of PI3-kinase. These results support the notion that Fyn may be directly involved in the activation of the downstream signaling enzyme, PI3-kinase, in IL-2-stimulated T cells.

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