ReferenceID 5976
Glycogen Synthase Kinase-3β Facilitates Cytokine Production in 12-O-Tetradecanoylphorbol-13-Acetate/Ionomycin-Activated Human CD4+ T Lymphocytes
Cells
Cytokines are the major immune regulators secreted from activated CD4+ T lymphocytes that activate adaptive immunity to eradicate nonself cells, including pathogens, tumors, and allografts. The regulation of glycogen syn
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Record Fields
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- Reference Id
- 5976
- Evidence Id
- 22566
- Core Evidence Id
- 22566
- Source Reference Id
- 5215
- Herb2 Reference Id
- HBREF006012
- Subject Paper Key
- HBIN039602_32521784
- Pubmed Id
- 32521784
- Doi
- 10.3390/cells9061424
- Paper Title
- Glycogen Synthase Kinase-3β Facilitates Cytokine Production in 12-O-Tetradecanoylphorbol-13-Acetate/Ionomycin-Activated Human CD4+ T Lymphocytes
- Paper Abstract
- Cytokines are the major immune regulators secreted from activated CD4+ T lymphocytes that activate adaptive immunity to eradicate nonself cells, including pathogens, tumors, and allografts. The regulation of glycogen synthase kinase (GSK)-3beta, a serine/threonine kinase, controls cytokine production by regulating transcription factors. The artificial in vitro activation of CD4+ T lymphocytes by a combination of 12-O-tetradecanoylphorbol-13-acetate and ionomycin, the so-called T/I model, led to an inducible production of cytokines, such as interferon-gamma, tumor necrosis factor-alpha, and interleukin-2. As demonstrated by the approaches of pharmacological targeting and genetic knockdown of GSK-3beta, T/I treatment effectively caused GSK-3beta activation followed by GSK-3beta-regulated cytokine production. In contrast, pharmacological inhibition of the proline-rich tyrosine kinase 2 and calcineurin signaling pathways blocked cytokine production, probably by deactivating GSK-3beta. The blockade of GSK-3beta led to the inhibition of the nuclear translocation of T-bet, a vital transcription factor of T lymphocyte cytokines. In a mouse model, treatment with the GSK-3beta inhibitor 6-bromoindirubin-3'-oxime significantly inhibited T/I-induced mortality and serum cytokine levels. In summary, targeting GSK-3beta effectively inhibits CD4+ T lymphocyte activation and cytokine production.
- Journal
- Cells
- Publish Year
- 2020
- Experiment Subject
- mouse
- Experiment Type
- Animal Experiment
- Phenotype Related
- Tumors
- Paper Title Cn
- Paper Title En
- Glycogen Synthase Kinase-3β Facilitates Cytokine Production in 12-O-Tetradecanoylphorbol-13-Acetate/Ionomycin-Activated Human CD4+ T Lymphocytes
- Bilingual Status
- semi_complete