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Series GSE8687 Query DataSets for GSE8687
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
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
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.
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 Jan 08, 2019
Contact name Mariusz Wasik
Organization name University of Pennsylvania
Department Pathology
Street address 3620 Hamilton Walk
City Philadelphia
State/province PA
ZIP/Postal code 19104
Country USA
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (12)
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
BioProject PRJNA101903

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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
Raw data provided as supplementary file

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