ArticleMolecular and cellular biology2000
Macrophages require constitutive NF-kappaB activation to maintain A1 expression and mitochondrial homeostasis.
Article in Molecular and cellular biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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Who cites it
58 citing papers in PubMed, 149 citations in OpenAlex.
- Critical role for antiapoptotic Bcl-xL and Mcl-1 in human macrophage survival and cellular IAP1/2 (cIAP1/2) in resistance to HIV-Vpr-induced apoptosis.The Journal of biological chemistry · 2012Trial
- Neutrophil extracellular traps promote macrophage activation through Toll-like receptor engagement and PKA and NF-kB signaling pathways.Cell communication and signaling : CCS · 2026Article
- The alternative polyadenylation regulator CFIm25 promotes macrophage differentiation and activates the NF-κB pathway.Cell communication and signaling : CCS · 2025Article
- MyD88 protein destabilization mitigates NF-κB-dependent protection against macrophage apoptosis.Cell communication and signaling : CCS · 2024Article
- Apoptosis Regulation in Osteoarthritis and the Influence of Lipid Interactions.International journal of molecular sciences · 2023Review
- Fluorinated polyamidoamine dendrimer-mediated miR-23b delivery for the treatment of experimental rheumatoid arthritis in rats.Nature communications · 2023Article
- NF-κB in monocytes and macrophages - an inflammatory master regulator in multitalented immune cells.Frontiers in immunology · 2023Review
- Inflammatory-associated apoptotic markers: are they the culprit to rheumatoid arthritis pain?Molecular biology reports · 2022Review
- Cytokine/Chemokine Release Patterns and Transcriptomic Profiles of LPS/IFNγ-Activated Human Macrophages Differentiated with Heat-KilledInternational journal of molecular sciences · 2021Article
- Reduced apoptosis of monocytes and macrophages is associated with their persistence in wounds of diabetic mice.Cytokine · 2021Article
- TAK1-AMPK Pathway in Macrophages Regulates Hypothyroid Atherosclerosis.Cardiovascular drugs and therapy · 2021Article
- Histone deacetylase 3 controls lung alveolar macrophage development and homeostasis.Nature communications · 2020Article
- The Role of Notch3 Signaling in Kidney Disease.Oxidative medicine and cellular longevity · 2020Review
- Elevated pre-activation basal level of nuclear NF-κB in native macrophages accelerates LPS-induced translocation of cytosolic NF-κB into the cell nucleus.Scientific reports · 2019Article
- Cell Type-Specific Roles of NF-κB Linking Inflammation and Thrombosis.Frontiers in immunology · 2019Review
- Impact of polyphenols in phagocyte functions.Journal of inflammation research · 2019Article
- Macrophage migration inhibitory factor regulates mitochondrial dynamics and cell growth of human cancer cell lines through CD74-NF-κB signaling.The Journal of biological chemistry · 2018Article
- FOXO3-dependent apoptosis limits alcohol-induced liver inflammation by promoting infiltrating macrophage differentiation.Cell death discovery · 2018Article
- Benzo(a)pyrene in Cigarette Smoke Enhances HIV-1 Replication through NF-κB Activation via CYP-Mediated Oxidative Stress Pathway.Scientific reports · 2018Article
- Intracellular apoptotic pathways: a potential target for reducing joint damage in rheumatoid arthritis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
NF-kappaB is a critical mediator of macrophage inflammatory responses, but its role in regulating macrophage survival has yet to be elucidated. Here, we demonstrate that constitutive NF-kappaB activation is essential for macrophage survival. Blocking the constitutive activation of NF-kappaB with pyrrolidine dithiocarbamate or expression of IkappaBalpha induced apoptosis in macrophagelike RAW 264.7 cells and primary human macrophages. This apoptosis was independent of additional death-inducing stimuli, including Fas ligation. Suppression of NF-kappaB activation induced a time-dependent loss of mitochondrial transmembrane potential (DeltaPsi(m)) and DNA fragmentation. Examination of initiator caspases revealed the cleavage of caspase 9 but not caspase 8 or the effector caspase 3. Addition of a general caspase inhibitor, z-VAD. fmk, or a specific caspase 9 inhibitor reduced DNA fragmentation but had no effect on DeltaPsi(m) collapse, indicating this event was caspase independent. To determine the pathway leading to mitochondrial dysfunction, analysis of Bcl-2 family members established that only A1 mRNA levels were reduced prior to DeltaPsi(m) loss and that ectopic expression of A1 protected against cell death following inactivation of NF-kappaB. These data suggest that inhibition of NF-kappaB in macrophages initiates caspase 3-independent apoptosis through reduced A1 expression and mitochondrial dysfunction. Thus, constitutive NF-kappaB activation preserves macrophage viability by maintaining A1 expression and mitochondrial homeostasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.