NF-κB in monocytes and macrophages – an inflammatory master regulator in multitalented immune cells

Abstract

Nuclear factor κB (NF-κB) is a dimeric transcription factor constituted by two of five protein family members. It plays an essential role in inflammation and immunity by regulating the expression of numerous chemokines, cytokines, transcription factors, and regulatory proteins. Since NF-κB is expressed in almost all human cells, it is important to understand its cell type-, tissue-, and stimulus-specific roles as well as its temporal dynamics and disease-specific context. Although NF-κB was discovered more than 35 years ago, many questions are still unanswered, and with the availability of novel technologies such as single-cell sequencing and cell fate-mapping, new fascinating questions arose. In this review, we will summarize current findings on the role of NF-κB in monocytes and macrophages. These innate immune cells show high plasticity and dynamically adjust their effector functions against invading pathogens and environmental cues. Their versatile functions can range from antimicrobial defense and antitumor immune responses to foam cell formation and wound healing. NF-κB is crucial for their activation and balances their phenotypes by finely coordinating transcriptional and epigenomic programs. Thereby, NF-κB is critically involved in inflammasome activation, cytokine release, and cell survival. Macrophage-specific NF-κB activation has far-reaching implications in the development and progression of numerous inflammatory diseases. Moreover, recent findings highlighted the temporal dynamics of myeloid NF-κB activation and underlined the complexity of this inflammatory master regulator. This review will provide an overview of the complex roles of NF-κB in macrophage signal transduction, polarization, inflammasome activation, and cell survival.

A single-cell atlas of ABCA7 loss-of-function reveals lipid disruptions, mitochondrial dysfunction and DNA damage in neurons

“…S10A; Data S12 ). Since NF-kB is a transcriptional master regulator of innate immune signaling ( 48 , 49 ), we next validated changes of the NF-kB subunit p65, whose localization to the nucleus is indicative of NF-kB activation. We stained PFC brain tissue for p65 and examined whether we could detect differences in intensity within NeuN surfaces.…”

Efficient and Targeted siRNA Delivery to M2 Macrophages by Smart Polymer Blends for M1 Macrophage Repolarization as a Promising Strategy for Future Cancer Treatment

“…Previous work by Ortega had already demonstrated the potential to alter macrophage phenotypes through NF-κB activation via IκBα knockdown . NF-κB is a well-known regulator of macrophage polarization and is associated with the development of the antitumoral M1 macrophage phenotype . We leveraged the same pathway to gain further insights into the formulation’s ability to induce macrophage repolarization, activating the NF-κB signaling molecule.…”

“…12 NF-κB is a well-known regulator of macrophage polarization and is associated with the development of the antitumoral M1 macrophage phenotype. 44 We leveraged the same pathway to gain further insights into the formulation's ability to induce macrophage repolarization, activating the NF-κB signaling molecule. Our results as shown by the western blot in Figure 8b indicated that neither the use of methyl-PEGylated instead of Man-PEG−PCL nor the mannan-blocked sample exhibited efficient NF-κB activation when compared to the use of the Man-PEG−PCL bNP formulation.…”

L-AP Alleviates Liver Injury in Septic Mice by Inhibiting Macrophage Activation via Suppressing NF-κB and NLRP3 Inflammasome/Caspase-1 Signal Pathways

“…It is also crucial for macrophages and other innate immunocytes to coordinate the inflammatory reactions against pathogens. 15,16 Under normal physiological conditions, NF-κB and its endogenous inhibitor, IκB, form a complex in the cytoplasm of macrophages and inhibit its nuclear translocation. 17 When macrophages are stimulated by pathogens, IKK phosphorylates IκB to form p-IκB and separate it from the IκB-NF-κB complex, and then NF-κB is phosphorylated and moves into the nucleus to induce the transcription of various inflammatory factors including IL-1β, IL-6, and IL-18, triggering cytokine storms.…”