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Status |
Public on Feb 19, 2008 |
Title |
Inhibition of activation of Sez-4 cell line with IL-2 by Jak kinase inhibitors. |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
In this study we compared the effects of IL-2, IL-15, and IL-21 on the gene expression, activation of cell signaling pathways, and functional properties of cells derived from the CD4+ cutaneous T-cell lymphoma (CTCL). Whereas both IL-2 and IL-15 that signal through receptors that share the common gamma chain and the beta chain modulated the expression of >1,000 genes, IL-21 that signals via the receptor also containing gamma chain up-regulated <40 genes. All three cytokines induced tyrosine phosphorylation of Jak1 and Jak3. However, only IL-2 and IL-15 strongly activated STAT5, PI3K/Akt, and MEK/ERK signaling pathways. In contrast, IL-21 selectively activated STAT3. Whereas all three cytokines protected CTCL cells from apoptosis, only IL-2 and IL-15 promoted their proliferation. The effects of the cytokine stimulation were Jak3- and Jak1-kinase dependent. These findings document the vastly different impact of IL-2 and IL-15 vs. IL-21 on malignant CD4+ T cells. They also suggest two novel therapeutic approaches to CTCL and, possibly, other CD4+ T cell lymphomas: inhibition of the Jak1/Jak3 kinase complex and, given the known strong immunostimulatory properties of IL-21 on CD8+ T, NK, and B cells, application of this cytokine to boost an immune response against malignant CD4+ T cells. Keywords: 3 replicates in each of 4 conditions
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Overall design |
Sez-4 cell line was starved of IL-2 for 16h, washed twice and placed into 6-well plates in 10ml RPMI (10% FBS) for 2h followed by pre-treating for 30’ with pan-Jak inhibitor (300 nM), Jak3 inhibitor (300 nM), or drig solvent and cultured with IL-2 (200U) or medium alone for 4 h.
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Contributor(s) |
Marzec M, Halasa K, Kasprzycka M, Wysocka M, Liu X, Tobias JW, Baldwin D, Zhang Q, Odum N, Rook AH, Wasik MA |
Citation(s) |
18281483 |
Submission date |
Aug 03, 2007 |
Last update date |
Mar 25, 2019 |
Contact name |
Mariusz Wasik |
Organization name |
University of Pennsylvania
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Department |
Pathology
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Street address |
3620 Hamilton Walk
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City |
Philadelphia |
State/province |
PA |
ZIP/Postal code |
19104 |
Country |
USA |
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Platforms (1) |
GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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Samples (12)
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GSM215361 |
Sez-4 cell line starved of IL-2 biological rep1 |
GSM215362 |
Sez-4 cell line starved of IL-2 biological rep2 |
GSM215363 |
Sez-4 cell line starved of IL-2 biological rep3 |
GSM215364 |
Sez-4 cell line starved of IL-2 and activated with IL-2 biological rep1 |
GSM215365 |
Sez-4 cell line starved of IL-2 and activated with IL-2 biological rep2 |
GSM215366 |
Sez-4 cell line starved of IL-2 and activated with IL-2 biological rep3 |
GSM215367 |
Sez-4 cell line starved of IL-2, pre-treated with pan-Jak inhibitor and activated with IL-2 biological rep1 |
GSM215368 |
Sez-4 cell line starved of IL-2, pre-treated with pan-Jak inhibitor and activated with IL-2 biological rep2 |
GSM215369 |
Sez-4 cell line starved of IL-2, pre-treated with pan-Jak inhibitor and activated with IL-2 biological rep3 |
GSM215370 |
Sez-4 cell line starved of IL-2, pre-treated with Jak3 inhibitor and activated with IL-2 biological rep1 |
GSM215371 |
Sez-4 cell line starved of IL-2, pre-treated with Jak3 inhibitor and activated with IL-2 biological rep2 |
GSM215372 |
Sez-4 cell line starved of IL-2, pre-treated with Jak3 inhibitor and activated with IL-2 biological rep3 |
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Relations |
BioProject |
PRJNA101903 |
Supplementary file |
Size |
Download |
File type/resource |
GSE8687_RAW.tar |
52.5 Mb |
(http)(custom) |
TAR (of CEL, EXP) |
Processed data included within Sample table |
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