ArticleThe Journal of biological chemistry2001
Ligation of CD40 stimulates the induction of nitric-oxide synthase in microglial cells.
Article in The Journal of biological chemistry, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 115 citations in OpenAlex.
- Systolic pressure overload caused pulmonary oxidative stress, vessel remodeling and severe microvascular thrombosis in CD40 knockout mice through promoting platelet aggregation.Redox biology · 2026Article
- Advances in the Role of the CD40-CD154 Pathway in the Pathogenesis of Diabetic Retinopathy.International journal of molecular sciences · 2026Review
- Corrected Version: Neutralization of RANTES and Eotaxin Prevents the Loss of Dopaminergic Neurons in a Mouse Model of Parkinson's Disease.Journal of clinical & experimental immunology · 2026Article
- CD40-CD154 Interactions Induced Progressive Neurodegeneration in Acute Ocular Hypertension Mice.Investigative ophthalmology & visual science · 2025Article
- Interleukin 6 and cancer resistance in glioblastoma multiforme.Neurosurgical review · 2024Review
- Article
- Arterial Baroreflex Dysfunction Promotes Neuroinflammation by Activating the Platelet CD40L/Nuclear Factor Kappa B Signaling Pathway in Microglia and Astrocytes.Neurochemical research · 2023Article
- Inducible nitric oxide synthase deficiency promotes murine-β-coronavirus induced demyelination.Virology journal · 2023Article
- Upregulation of IL-1 Receptor Antagonist by Aspirin in Glial Cells via Peroxisome Proliferator-Activated Receptor-Alpha.Journal of Alzheimer's disease reports · 2021Article
- Training of Primary Chicken Monocytes Results in Enhanced Pro-Inflammatory Responses.Veterinary sciences · 2020Article
- Low-Dose Maraviroc, an Antiretroviral Drug, Attenuates the Infiltration of T Cells into the Central Nervous System and Protects the Nigrostriatum in Hemiparkinsonian Monkeys.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- TGF-β1 Neuroprotection via Inhibition of Microglial Activation in a Rat Model of Parkinson's Disease.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2017Article
- Induction of Adaptive Immunity Leads to Nigrostriatal Disease Progression in MPTP Mouse Model of Parkinson's Disease.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Myeloid C/EBPβ deficiency reshapes microglial gene expression and is protective in experimental autoimmune encephalomyelitis.Journal of neuroinflammation · 2017Article
- T Cell Cancer Therapy Requires CD40-CD40L Activation of Tumor Necrosis Factor and Inducible Nitric-Oxide-Synthase-Producing Dendritic Cells.Cancer cell · 2016Article
- Neutralization of RANTES and Eotaxin Prevents the Loss of Dopaminergic Neurons in a Mouse Model of Parkinson Disease.The Journal of biological chemistry · 2016Article
- Interleukin-10 Protection against Lipopolysaccharide-Induced Neuro-Inflammation and Neurotoxicity in Ventral Mesencephalic Cultures.International journal of molecular sciences · 2015Article
- Soluble CD40 Ligand in Sera of Subjects Exposed to Leishmania infantum Infection Reduces the Parasite Load in Macrophages.PloS one · 2015Article
- Benfotiamine upregulates antioxidative system in activated BV-2 microglia cells.Frontiers in cellular neuroscience · 2015Article
- CD40 promotes the development of early diabetic retinopathy in mice.Diabetologia · 2014Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The present study was undertaken to investigate the role of CD40 ligation in the expression of inducible nitric-oxide synthase (iNOS) in mouse BV-2 microglial cells and primary microglia. Ligation of CD40 alone by either cross-linking antibodies against CD40 or a recombinant CD40 ligand (CD154) was unable to induce the production of NO in BV-2 microglial cells. The absence of induction of NO production by CD40 ligation alone even in CD40-overexpressed BV-2 microglial cells suggests that a signal transduced by the ligation of CD40 alone is not sufficient to induce NO production. However, CD40 ligation markedly stimulated interferon-gamma (IFN-gamma)-mediated NO production. Ligation of CD40 in CD40-overexpressed cells further stimulated IFN-gamma-induced production of NO. This stimulation of NO production was accompanied by stimulation of the iNOS protein and mRNA. In addition to BV-2 glial cells, CD40 ligation also stimulated IFN-gamma-mediated NO production in mouse primary microglia and peritoneal macrophages. To understand the mechanism of induction/stimulation of iNOS, we investigated the roles of nuclear factor kappaB (NF-kappaB) and CCAAT/enhancer-binding protein beta (C/EBPbeta), transcription factors responsible for the induction of iNOS. IFN-gamma alone was able to induce the activation of NF-kappaB as well as C/EBPbeta. However, CD40 ligation alone induced the activation of only NF-kappaB but not of C/EBPbeta, suggesting that the activation of NF-kappaB alone by CD40 ligation is not sufficient to induce the expression of iNOS and that the activation of C/EBPbeta is also necessary for the expression of iNOS. Consistently, dominant-negative mutants of p65 (Deltap65) and C/EBPbeta (DeltaC/EBPbeta) inhibited the expression of iNOS in BV-2 microglial cells that were stimulated with the combination of IFN-gamma and CD40 ligand. Stimulation of IFN-gamma-mediated activation of NF-kappaB but not of C/EBPbeta by CD40 ligation suggests that CD40 ligation stimulates the expression of iNOS in IFN-gamma-treated BV-2 microglial cells through the stimulation of NF-kappaB activation. This study illustrates a novel role for CD40 ligation in stimulating the expression of iNOS in microglial cells, which may participate in the pathogenesis of neuroinflammatory diseases.
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