Glycogen synthase kinase 3β (GSK3B); NF-κB; nuclear factor of κ light polypeptide gene enhancer in B cells 2 p49/p100 (NFKB2; p52)

2012 ◽  
Vol 5 (11) ◽  
pp. 279-279
Keyword(s):  
B Cells ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Nuclear Factor ◽  
Glycogen Synthase Kinase 3Β ◽  
Gene Enhancer

scholarly journals Inhibition of Glycogen Synthase Kinase 3β Increases the Proportion and Suppressive Function of CD19+CD24hiCD27+ Breg Cells

2020 ◽  
Vol 11 ◽  
Author(s):  
Jinyang Li ◽  
Ji Gao ◽  
Haoming Zhou ◽  
Jinren Zhou ◽  
Zhenghua Deng ◽  
...  
Keyword(s):  
B Cells ◽  
Glycogen Synthase ◽  
Inflammatory Diseases ◽  
Adaptive Immune System ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β ◽  
Activated T Cells ◽  
Novel Strategy ◽  
Gsk 3Β

CD19+CD24hiCD27+ memory Breg cells exhibit decreased abundance in patients with chronic graft-versus-host disease (cGVHD) after liver transplantation and produce less IL-10 than those from patients without cGVHD and healthy donors. Due to the lack of Breg cells and the difficulty in expanding them in vitro, in mouse models and early human clinical trials, the adoptive transfer of Breg cells to autoimmune diseases is greatly restricted. Glycogen synthase kinase 3β (GSK-3β) is a multifunctional serine/threonine (ser/thr) protein kinase that can participate in B cell growth, metabolic activity, and proliferation. Phosphoprotein array analysis showed that p-GSK-3β-s9 was highly expressed in mBreg cells. Furthermore, here, we demonstrated that GSK-3β expression in mBreg cells is lower than that observed in B cells by flow cytometry. We found that the treatment of B cells with the specific GSK-3β inhibitor SB216763 can significantly increase the proportion and immunosuppressive function of mBreg cells in vitro. Nuclear factor of activated T cells (NFAT) is one of a pivotal regulator of gene expression in adaptive immune system. Here, we observed that inhibition of GSK-3β by SB216763 results in enhanced expression of NFATc1 in B cells, which is essential in regulating the ability of B cells to secrete IL-10. By constructing a xGVHD mouse model, we observed that SB216763-treated mBreg cells effectively prevent xenogeneic GVHD. Here we propose a novel strategy using SB216763 to inhibit GSK-3β and then enhance the proportion and immunosuppressive function of mBreg cells by increasing the expression of NFATc1. This approach may be used as a therapy to ameliorate GVHD and inflammatory diseases.

Glycogen synthase kinase-3β indirectly facilitates interferon-γ-induced nuclear factor-κB activation and nitric oxide biosynthesis

2010 ◽  
Vol 111 (6) ◽  
pp. 1522-1530 ◽  
Author(s):  
Jui-In Kai ◽  
Wei-Ching Huang ◽  
Cheng-Chieh Tsai ◽  
Wen-Teng Chang ◽  
Chia-Ling Chen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Glycogen Synthase ◽  
Nuclear Factor Κb ◽  
Interferon Γ ◽  
Glycogen Synthase Kinase ◽  
Nuclear Factor ◽  
Glycogen Synthase Kinase 3Β

scholarly journals Glycogen Synthase Kinase 3β-Mediated Apoptosis of Primary Cortical Astrocytes Involves Inhibition of Nuclear Factor κB Signaling

2003 ◽  
Vol 23 (13) ◽  
pp. 4649-4662 ◽  
Author(s):  
Joseph F. Sanchez ◽  
Lynn F. Sniderhan ◽  
Andrea L. Williamson ◽  
Shongshan Fan ◽  
Shikha Chakraborty-Sett ◽  
...  
Keyword(s):  
Cell Fate ◽  
Glycogen Synthase ◽  
Nuclear Factor Κb ◽  
Glycogen Synthase Kinase ◽  
Nuclear Factor ◽  
Glycogen Synthase Kinase 3Β ◽  
Inhibitory Protein ◽  
Cortical Astrocytes ◽  
Iκb Kinase ◽  
Gsk 3Β

ABSTRACT Recent studies have revealed a positive correlation between astrocyte apoptosis and rapid disease progression in persons with neurodegenerative diseases. Glycogen synthase kinase 3β (GSK-3β) is a molecular regulator of cell fate in the central nervous system and a target of the phosphatidylinositol 3-kinase (PI-3K) pathway. We have therefore examined the role of the PI-3K pathway, and of GSK-3β, in regulating astrocyte survival. Our studies indicate that inhibition of PI-3K leads to apoptosis in primary cortical astrocytes. Furthermore, overexpression of a constitutively active GSK-3β mutant (S9A) is sufficient to cause astrocyte apoptosis, whereas an enzymatically inactive GSK-3β mutant (K85M) has no effect. In light of reports on the interplay between GSK-3β and nuclear factor κB (NF-κB), and because of the antiapoptotic activity of NF-κB, we examined the effect of GSK-3β overexpression on NF-κB activation. These experiments revealed strong inhibition of NF-κB activation in astrocytes upon overexpression of the S9A, but not the K85M, mutant of GSK-3β. This was accompanied by stabilization of the NF-κB-inhibitory protein, IκBα and down-regulation of IκB kinase (IKK) activity. These findings therefore implicate GSK-3β as a regulator of NF-κB activation in astrocytes and suggest that the pro-apoptotic effects of GSK-3β may be mediated at least in part through the inhibition of NF-κB pathway.

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