ArticleMolecular and cellular biology2005
Essential role of STAT1 in caspase-independent cell death of activated macrophages through the p38 mitogen-activated protein kinase/STAT1/reactive oxygen species pathway.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 75 citations in OpenAlex.
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- Enhancement of Autophagy in Macrophages via the p120-Catenin-Mediated mTOR Signaling Pathway.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Modulation of Innate Immune Memory Dynamics by Subcellular Reactive Oxygen Species.Antioxidants & redox signaling · 2023Review
- Pan-Caspase Inhibitor zVAD Induces Necroptotic and Autophagic Cell Death in TLR3/4-Stimulated Macrophages.Molecules and cells · 2022Article
- Urolithin A Inactivation of TLR3/TRIF Signaling to Block the NF-κB/STAT1 Axis Reduces Inflammation and Enhances Antioxidant Defense in Poly(I:C)-Induced RAW264.7 Cells.International journal of molecular sciences · 2022Article
- Nrf2-mediated anti-inflammatory polarization of macrophages as therapeutic targets for osteoarthritis.Frontiers in immunology · 2022Review
- Article
- Development of Exhausted Memory Monocytes and Underlying Mechanisms.Frontiers in immunology · 2021Article
- Reactive Oxygen Species in Macrophages: Sources and Targets.Frontiers in immunology · 2021Review
- Recent advances in dead cell clearance during acute lung injury and repair.Faculty reviews · 2021Review
- Plant chemical genetics reveals colistin sulphate as a SA and NPR1-independent PR1 inducer functioning via a p38-like kinase pathway.Scientific reports · 2019Article
- Organophosphate pesticide chlorpyrifos impairs STAT1 signaling to induce dopaminergic neurotoxicity: Implications for mitochondria mediated oxidative stress signaling events.Neurobiology of disease · 2018Article
- ERK is a negative feedback regulator for IFN-γ/STAT1 signaling by promoting STAT1 ubiquitination.BMC cancer · 2018Article
- Reactive oxygen species-induced parthanatos of immunocytes by human cytomegalovirus-associated substance.Microbiology and immunology · 2018Article
- Photodynamic therapy combined to cisplatin potentiates cell death responses of cervical cancer cells.BMC cancer · 2017Article
- Interferon Potentiates Toll-Like Receptor-Induced Prostaglandin DFrontiers in immunology · 2017Article
- Myricitrin Modulates NADPH Oxidase-Dependent ROS Production to Inhibit Endotoxin-Mediated Inflammation by Blocking the JAK/STAT1 and NOX2/p47Oxidative medicine and cellular longevity · 2017Article
- Article
- Autophagy deficiency in myeloid cells increases susceptibility to obesity-induced diabetes and experimental colitis.Autophagy · 2016Article
- Integrating Immunologic Signaling Networks: The JAK/STAT Pathway in Colitis and Colitis-Associated Cancer.Vaccines · 2016Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Unlike other immune cells, activation of macrophages by stimulating agents, such as lipopolysaccharide (LPS), confers significant resistance to many apoptotic stimuli, but the underlying mechanism of this phenomenon remains largely unknown. Here, we demonstrate that LPS-induced early caspase activation is essential for macrophage survival because blocking caspase activation with a pancaspase inhibitor (zVAD [benzyloxycarbonyl-Val-Ala-Asp]) rapidly induced death of activated macrophages. This type of death process by zVAD/LPS was principally mediated by intracellular generation of superoxide. STAT1 knockout macrophages demonstrated profoundly decreased superoxide production and were resistant to treatment with zVAD/LPS, indicating the crucial involvement of STAT1 in macrophage death by zVAD/LPS. STAT1 level and activity were reciprocally regulated by caspase activation and were associated with cell death. Activation of STAT1 was critically dependent upon serine phosphorylation induced by p38 mitogen-activated protein kinase (MAPK) because a p38 MAPK inhibitor nullified STAT1 serine phosphorylation, reactive oxygen species (ROS) production, and macrophage death by zVAD/LPS. Conversely, p38 MAPK activation was dependent upon superoxide and was also nullified in STAT1 knockout macrophages, probably due to impaired generation of superoxide. Our findings collectively indicate that STAT1 signaling modulates intracellular oxidative stress in activated macrophages through a positive-feedback mechanism involving the p38 MAPK/STAT1/ROS pathway, which is interrupted by caspase activation. Furthermore, our study may provide significant insights in regards to the unanticipated critical role of STAT1 in the caspase-independent death pathway.
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