Search results for "B-Cell Lymphoma 3 Protein"
showing 3 items of 3 documents
Hepatic B cell leukemia-3 promotes hepatic steatosis and inflammation through insulin-sensitive metabolic transcription factors.
2016
Background & Aims The pathomechanisms underlying non-alcoholic fatty liver disease (NAFLD) and the involved molecular regulators are incompletely explored. The nuclear factor-kappa B (NF-κB)-cofactor gene B cell leukemia-3 ( Bcl-3 ) plays a critical role in altering the transcriptional capacity of NF-κB – a key inducer of inflammation – but also of genes involved in cellular energy metabolism. Methods To define the role of Bcl-3 in non-alcoholic steatohepatitis (NASH), we developed a novel transgenic mouse model with hepatocyte-specific overexpression of Bcl-3 ( Bcl-3 Hep ) and employed a high-fat, high-carbohydrate dietary feeding model. To characterize the transgenic model, deep RNA seque…
Elevated levels of Bcl-3 inhibits Treg development and function resulting in spontaneous colitis
2017
Bcl-3 is an atypical NF-κB family member that regulates NF-κB-dependent gene expression in effector T cells, but a cell-intrinsic function in regulatory T (Treg) cells and colitis is not clear. Here we show that Bcl-3 expression levels in colonic T cells correlate with disease manifestation in patients with inflammatory bowel disease. Mice with T-cell-specific overexpression of Bcl-3 develop severe colitis that can be attributed to defective Treg cell development and function, leading to the infiltration of immune cells such as pro-inflammatory γδT cells, but not αβ T cells. In Treg cells, Bcl-3 associates directly with NF-κB p50 to inhibit DNA binding of p50/p50 and p50/p65 NF-κB dimers, t…
Overexpression of Bcl-3 inhibits the development of marginal zone B cells.
2013
The transcription factor Bcl-3 functions as a proto-oncogene via regulation of cell proliferation and apoptosis. Bcl-3 is an atypical member of the IκB family and plays a central role in the immune response through interactions with the NF-κB subunits p50 and p52. To investigate the impact of Bcl-3 on B-cell maturation and regulation, we generated mice that overexpress Bcl-3 specifically in B cells. Interestingly, these mice lack marginal zone B cells and exhibit a significant reduction in the number of B-1 B cells. Further, B cells from these mice are impaired in their proliferative capacity. Our data demonstrate that the overexpression of the transcription factor Bcl-3 inhibits germinal c…