nuclear factor kappa B

Overview

Nuclear factor kappa B (NF-κB) is a family of pleiotropic transcription factors that serve as master regulators of inflammatory, immune, and cell survival responses across virtually all mammalian cell types. The NF-κB family comprises five members — RelA (p65), RelB, c-Rel, p50, and p52 — which form homo- or heterodimeric complexes that, in their inactive state, are sequestered in the cytoplasm by inhibitory proteins known as IκB (inhibitor of κB). Canonical NF-κB activation is triggered by a wide range of stimuli including pathogen-associated molecular patterns, proinflammatory cytokines such as Tumour necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β), oxidative stress, and receptor signaling. Upon activation, the IκB kinase (IKK) complex phosphorylates IκBα, targeting it for proteasomal degradation and releasing the NF-κB dimer to translocate to the nucleus, where it drives transcription of genes encoding cytokines, adhesion molecules, anti-apoptotic factors, and other inflammatory mediators. A non-canonical (alternative) pathway additionally exists, relying on IKKα-mediated processing of p100 to p52, and is implicated in lymphoid organogenesis and specific immune contexts.

The biological significance of NF-κB is underscored by its convergence with virtually every major signaling network in human disease. It cross-talks extensively with the MAPK cascade, the PI3K/Akt signaling pathway, the JAK-STAT axis, the NLRP3 inflammasome, toll-like receptor (TLR) signaling, and the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway. Dysregulated NF-κB activity has been mechanistically implicated in a broad spectrum of conditions spanning chronic inflammatory disorders, neurodegeneration, autoimmunity, metabolic disease, and cancer. This centrality makes NF-κB one of the most intensively studied signaling nodes in biomedical research, serving simultaneously as a mechanistic readout of disease pathology and as a high-priority therapeutic target.

Focus of Latest Publications

Recent publications consistently positioned NF-κB as a central inflammatory and stress-response node across diverse disease models. In gastric inflammation driven by Helicobacter pylori, NF-κB was examined alongside p38-MAPK, ERK1/2, and JNK as part of inflammatory signaling downstream of LOX-1. In diabetes-related studies, NF-κB suppression was reported in the context of honokiol-loaded solid lipid nanoparticles in STZ-induced type 1 diabetes, where reduced NF-κB signaling accompanied antioxidant effects and decreased apoptosis. A separate study in type 2 diabetic nephropathy compared NF-κB expression with PXDN as a potential diagnostic biomarker, highlighting its association with oxidative stress and renal injury.

NF-κB also appeared repeatedly in neuroinflammation and neuroprotection research. In amyloid-β-induced Alzheimer’s disease models, hippocampal NF-κB expression was measured by real-time PCR, and multiple interventions were reported to reduce NF-κB-associated inflammatory signaling, including abscisic acid, lawsone, myrtenol, loganic acid, and electroacupuncture via the SIRT1-NF-κB axis. In spinal cord injury and neuropathic pain models, indole-3-propionic acid, herkinorin, and IL-6R-CD3-engineered regulatory T cells were associated with suppression of NF-κB and related MAPK signaling, suggesting attenuation of astrocyte and microglial activation. Carboplatin was also reported to inhibit NF-κB phosphorylation in TDP-43-transfected astrocytes, reducing pro-inflammatory cytokine production.

In gastrointestinal, hepatic, and metabolic inflammation, NF-κB was repeatedly identified as a mechanistic target. Quinoa bran polysaccharides, Melissa officinalis extract, naringin, mulberry leaf extracts, chestnut wood extract, and coffee pulp extract were all linked to inhibition of NF-κB signaling in colitis, reflux esophagitis, autoimmune hepatitis, non-alcoholic fatty liver disease, and intestinal oxidative stress models. In diabetic liver injury, TNF-α was reported to promote pyroptosis through the HMGB1/TLR4/MyD88/NF-κB pathway. In diabetic foot ulcer, NF-κB pathway enrichment was associated with disease progression, while in diabetic wound management, glabridin-containing eutectogel was reported to inhibit NF-κB and promote macrophage polarization from M1 to M2.

NF-κB was also central in musculoskeletal and bone-related pathology. In aging-related periodontitis, fibroblast activation protein triggered NF-κB signaling in senescent gingival fibroblasts, driving osteoclastogenesis and inflammatory bone resorption. Curcumin attenuated hindlimb unloading-induced bone loss by suppressing NF-κB-mediated osteoclast activation, and molybdenum nanodots were reported to reprogram inflammatory osteolysis by curbing NF-κB-mediated M1 macrophage polarization. In intervertebral disc degeneration, aucubin and tanshinol were reported to inhibit NF-κB activation in nucleus pulposus cells.

Several studies linked NF-κB to macrophage polarization and innate immune remodeling. High-salt diet was described as activating NF-κB and NLRP3 signaling in macrophage-associated metabolic disorders, promoting a proinflammatory M1 phenotype. IL-4 was reported to facilitate M2 polarization through the NF-κB/IκB pathway in polycystic ovary syndrome. In coronary artery disease, the FVIIa/TF coagulation complex and PAR2 were shown to activate NF-κB in monocytes, aggravating inflammation. In allergic rhinitis, rosacea, and radiation pneumonitis, NF-κB suppression was repeatedly associated with reduced inflammatory mediator release and improved tissue outcomes.

Cancer-related studies also highlighted NF-κB as a pro-survival and immunomodulatory pathway. In colorectal cancer, EFHD2-driven lactate was reported to activate NF-κB signaling, contributing to immunosuppression and radioresistance. Another colorectal cancer study suggested that an 8-sulfonamidoquinoline compound may inhibit NF-κB by binding p65. In lung adenocarcinoma, an SLC2A1-associated malignant epithelial cell state was characterized by NF-κB activation and an immunosuppressive tumor microenvironment. In invasive lobular carcinoma, LOX inhibition downregulated NF-κB transcriptional programs, and in gastric cancer, chiral bismuth molybdate nanoparticles activated NF-κB in splenic macrophages as part of an immune-stimulatory mechanism.

Across these studies, NF-κB was most often treated as a downstream readout of inflammatory activation or as a therapeutic target for pathway inhibition. The recurring pattern was that interventions with plant-derived compounds, probiotics, nanoparticles, electroacupuncture, and engineered biologics reduced NF-κB phosphorylation, nuclear translocation, or expression of NF-κB-associated inflammatory mediators such as TNF-α, IL-1β, IL-6, iNOS, COX-2, and NLRP3. In some settings, however, NF-κB activation was intentionally leveraged to stimulate immune responses, as in dendritic cell hyperactivation and macrophage-mediated antitumor effects.

Key Publications

• NEWMay Harnessing plant-derived bioactive compounds as LOX-1 inhibitors in Helicobacter pylori-driven gastric inflammation. (Toxicology and applied pharmacology, 2026, PMID 42128233): "Since LOX-1 is linked to inflammatory signalling pathways, we investigated the phosphorylation of p38-MAPK, ERK1/2, JNK, and NF-κB."
• NEWMar Oral Honokiol-loaded solid lipid nanoparticles: A shielding nanotherapeutic strategy to attenuate STZ-induced type 1 diabetes via targeted modulation of oxidative stress and apoptotic signaling. (Molecular and cellular endocrinology, 2026, PMID 41856197): "Additionally, it was demonstrated that Honokiol-SLNs inhibited apoptosis by reducing the expression of cleaved caspase-3, exhibited beneficial antioxidant properties by enhancing nuclear factor erythroid 2-related factor 2 (Nrf2), and mitigated inflammation by suppressing nuclear factor kappa B (NF-κB)."
• NEWApr Evaluation of the effects of ivermectin and Moringa oleifera nanoparticles on muscular trichinellosis in a murine model. (Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 2026, PMID 42035901): "In addition, the local immunohistochemical expression of nuclear factor-kappa B (NF-κB) in skeletal muscles was evaluated."
• Jul Oxidative Stress-Induced Expression Levels of PXDN and NF-κB in Type 2 Diabetic Patients With Nephropathy. (Endocrinology, diabetes & metabolism, 2026, PMID 42286730): "We also compared PXDN and Nuclear factor-κB (NF-κB) expression levels in DN patients, aiming to identify a reliable diagnostic biomarker."
• Jul Abscisic acid ameliorates cognitive deficits in an amyloid-β-induced mouse model of Alzheimer's disease associated with alterations in markers of neuroplasticity and neuroinflammation. (Neuroscience letters, 2026, PMID 42097395): "Hippocampal gene expression levels of brain-derived neurotrophic factor (BDNF), N-methyl-D-aspartate receptor (NMDAR), and nuclear factor-κB (NF-κB) were evaluated using real-time PCR."
• Jun EFHD2 drives lactate-mediated DNA damage repair and immunosuppression via HMGB1 and HIF-1α to confer radioresistance in colorectal cancer. (Cell death & disease, 2026, PMID 42336814): "Elevated EFHD2-driven lactate reshaped the tumor immune microenvironment by promoting M2 macrophage polarization, suppressing antigen presentation, activating nuclear factor kappa-B (NF-κB) signaling, and upregulating programmed death-ligand 1 (PD-L1)."
• Jun Multi-omics combined analysis of turmeric volatile oil alleviating allergic rhinitis through the JNK/MAPK-Relb/NF-κB pathway. (NPJ science of food, 2026, PMID 42310315): "Proteomic analysis using four-dimensional data-independent acquisition indicated that the mitogen-activated protein kinase (MAPK) and transcription factor nuclear factor-κB (NF-κB) signaling pathways are involved in TVO's anti-inflammatory mechanism."
• Jun Structural Characterization and Deconstruction of Polysaccharides from Chenopodium quinoa Willd. Bran: Mechanistic Insights into Their Protective Effects against Colitis. (Journal of agricultural and food chemistry, 2026, PMID 42044467): "It can alleviate tissue damage and inflammatory symptoms of colitis and inhibit the NF-κB signaling pathway."
• Jun Integrated multi-technology exploration of the mechanism by which Badushengji San regulates core targets in diabetic foot ulcer. (Molecular genetics and genomics : MGG, 2026, PMID 42298176): "These biomarkers were enriched in pathways like nuclear factor-kappa B (NF-κB), and their abnormal expression was closely linked to DFU pathological progression."
• Jun Inhibiting fibroblast activation protein mitigates aging-related periodontitis by blocking nuclear factor kappa B-mediated osteoclastogenesis. (International immunopharmacology, 2026, PMID 41966776): "Mechanistically, FAP activation in senescent gingival fibroblasts triggered the nuclear factor kappa B (NF-κB) signaling pathway (p<0.01), driving inflammatory bone resorption."