Bcl-3: A Double-Edged Sword in Immune Cells and Inflammation

Abstract

The NF-κB transcription factor family controls the transcription of many genes and regulates a number of pivotal biological processes. Its activity is regulated by the IκB family of proteins. Bcl-3 is an atypical member of the IκB protein family that regulates the activity of nuclear factor NF-κB. It can promote or inhibit the expression of NF-κB target genes according to the received cell type and stimulation, impacting various cell functions, such as proliferation and differentiation, induction of apoptosis and immune response. Bcl-3 is also regarded as an environment-dependent cell response regulator that has dual roles in the development of B cells and the differentiation, survival and proliferation of Th cells. Moreover, it also showed a contradictory role in inflammation. At present, in addition to the work aimed at studying the molecular mechanism of Bcl-3, an increasing number of studies have focused on the effects of Bcl-3 on inflammation, immunity and malignant tumors in vivo. In this review, we focus on the latest progress of Bcl-3 in the regulation of the NF-κB pathway and its extensive physiological role in inflammation and immune cells, which may help to provide new ideas and targets for the early diagnosis or targeted treatment of various inflammatory diseases, immunodeficiency diseases and malignant tumors.

IL-10 dependent adaptation allows macrophages to adjust inflammatory responses to TLR4 stimulation history

“…However, phosphorylated BCL-3 might also facilitate activation of gene transcription by dissociating inhibitory p50 homodimers from regulatory gene elements [48, 49]. It is currently not yet clear if those contrasting roles of BCL-3 in gene regulation appear in parallel on the same or different genes or differ depending on the organism (for review, see [50]).…”

Ligustilide induces apoptosis and reduces proliferation in human bladder cancer cells by NFκB1 and mitochondria pathway

“…NFκB1 is a member of NF-κB family, and NFκB1 (p50) is the cleavage form of NFκB1 (p105) by proteasome, which takes part in the regulation of transcriptional activity (Yu et al, 2009). NFκB1 (p50) mainly inhibits cells apoptosis via the downregulation of the mRNA expression of some anti-apoptotic genes, such as Bcl-2, B-cell lymphoma-extra-large (Bcl-xl), X-linked inhibitor of apoptosis protein (XIAP), cellular inhibitor of apoptosis protein (cIAP), and FLICE-like inhibitory protein (FLIP) (Yu et al, 2009) (Liu et al, 2022). LIG significantly inhibited the protein levels of NFκB1 (p50) and may activate the subsequent signaling pathway to abrogate the inhibition of NFκB1 (p50) antiapoptotic ability.…”

Molecular Mechanisms of the Anti-Inflammatory Effects of Epigallocatechin 3-Gallate (EGCG) in LPS-Activated BV-2 Microglia Cells

“…The inhibitory action of EGCG on the NF-κB pathway as well as its actions to downregulate TRAFs (TRAFs 2, 3, and 5), allows for TLR to mediate TLR signaling (upregulation of TLRs 1, 3 and 4), thus reducing inflammatory cytokine production (CCL5 and IL-1b). EGCG also reduced bcl3 expression, which is involved in directing NF-κB activity [ 64 ] and lipid metabolism [ 65 ]. NF-κB analysis demonstrated SMAD3 upregulation, thus showing a connection to transforming growth factor beta (TGF-β), which may be another clearance mechanism utilized by EGCG in mediating aging and neurodegeneration.…”