NF-κB: At the Borders of Autoimmunity and Inflammation

Abstract

The transcription factor NF-κB regulates multiple aspects of innate and adaptive immune functions and serves as a pivotal mediator of inflammatory response. In the first part of this review, we discuss the NF-κB inducers, signaling pathways, and regulators involved in immune homeostasis as well as detail the importance of post-translational regulation by ubiquitination in NF-κB function. We also indicate the stages of central and peripheral tolerance where NF-κB plays a fundamental role. With respect to central tolerance, we detail how NF-κB regulates medullary thymic epithelial cell (mTEC) development, homeostasis, and function. Moreover, we elaborate on its role in the migration of double-positive (DP) thymocytes from the thymic cortex to the medulla. With respect to peripheral tolerance, we outline how NF-κB contributes to the inactivation and destruction of autoreactive T and B lymphocytes as well as the differentiation of CD4+-T cell subsets that are implicated in immune tolerance. In the latter half of the review, we describe the contribution of NF-κB to the pathogenesis of autoimmunity and autoinflammation. The recent discovery of mutations involving components of the pathway has both deepened our understanding of autoimmune disease and informed new therapeutic approaches to treat these illnesses.

Novel Insights into the Emerging Role of Neat1 and Its Effects Downstream in the Regulation of Inflammation

“…Nuclear factor-kB (NF-κB) is present in almost all types of cells and primarily serves as a transcription factor implicated in various biological processes, such as apoptosis, cell proliferation, tumorigenesis, inflammation, and various autoimmune disorders. 147 It is revealed to promote multiple proinflammatory mediators, and suppression of NF-κB signaling correlates with beneficial effects in inflammatory conditions. For instance, LncRNA Snhg8 acts as a competitive endogenous RNA (ceRNA) by binding to miR-425–5p, which was revealed to boost microglial inflammation by targeting the sirtuin1 (SIRT1)‐mediated NF‐κB pathway.…”

Extraction, Isolation and Characterization of Bioactive Compounds from Artemisia and Their Biological Significance: A Review

“…Thus, the inhibition of NF-κB minimizes inflammatory response and derails cancer proliferation. NF-κB involved in cellular responses to stimuli and has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development [50]. In a dose-dependent fashion, artemisinin precludes the "secretion of tumor necrosis factor (TNF)-α, interleukin-(IL-) 1β, and IL-6", which imparts an "antiinflammatory effect on phorbol myristate acetate-(PMA-) induced THP-1 human monocytes" [36].…”

Gill Transcriptomic Responses to Toxin-producing Alga Prymnesium parvum in Rainbow Trout

“…The presence of gill inflammation inferred from the gene expression changes in the fish exposed to P. parvum is also supported by the results of the IPA upstream regulator analysis (Figure 6, Supplementary Table 10). Specifically, 6 of the 10 common upstream regulators (all identified as activated) are known for their pro-inflammatory action, including TNF, TGFB1, IL-1B, IL-6, IFNG and NFkB complex, with TGFB1 and NFkB complex also contributing to mounting the anti-inflammatory response (73,(86)(87)(88)(89). The remaining 4 common upstream regulators have been linked to inhibition of inflammatory responses (PDGF BB), inflammation-induced coagulation (F2) and the growth, proliferation and differentiation of numerous cell types that are necessary for tissue repair and regeneration (HGF and EGF) (90)(91)(92).…”