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.

scholarly journals Signalling through CD28 T-cell activation pathway involves an inositol phospholipid-specific phospholipase C activity

1993 ◽  
Vol 293 (3) ◽  
pp. 835-842 ◽  
Author(s):  
J Nunes ◽  
S Klasen ◽  
M D Franco ◽  
C Lipcey ◽  
C Mawas ◽  
...  
Keyword(s):  
T Cell ◽  
Phospholipase C ◽  
T Cell Activation ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Jurkat Cells ◽  
Cd28 Molecule ◽  
Human T Cell ◽  
Protein Kinase C Inhibitor ◽  
Human T Cell Line

Stimulation of the human T-cell line, Jurkat, by a monoclonal antibody (mAb) directed against the CD28 molecule leads to sustained increases in intracellular levels of Ca2+ ([Ca2+]i); the initial rise in Ca2+ comes from internal stores, followed by Ca2+ entry into the cells. The CD28 molecule also appears to activate polyphosphoinositide (InsPL)-specific phospholipase C (PLC) activity in Jurkat cells, as demonstrated by PtdInsP2 breakdown, InsP3 and 1,2-diacylglycerol generation and PtdIns resynthesis. We also observed that interleukin-2 (IL2) production induced via CD28 triggering was sensitive to a selective protein kinase C inhibitor. Of the four other anti-CD28 mAbs (CD28.2, CD28.4, CD28.5, CD28.6) tested, only one (CD28.5) was unable to generate any InsPL-specific PLC or IL2 secretion. However, the cross-linking of cell-bound CD28.5 with anti-mouse Ig antibodies led to an increase in [Ca2+]i. CD28-molecule clustering in itself appears to be a sufficient signal for induction of PLC activity.

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

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

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.

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