ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Dyad of CD40/CD40 ligand fosters neuroinflammation at the blood-brain barrier and is regulated via JNK signaling: implications for HIV-1 encephalitis.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- The relationship between HIV-1 neuroinflammation, neurocognitive impairment and encephalitis pathology: A systematic review of studies investigating post-mortem brain tissue.Reviews in medical virology · 2024Pooled it
- Characterization of platelet-monocyte complexes in HIV-1-infected individuals: possible role in HIV-associated neuroinflammation.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Experimental challenge of African green monkeys with contemporary Hendra virus isolates produces divergent clinical disease.Emerging microbes & infections · 2025Article
- Schizophrenia endothelial cells exhibit higher permeability and altered angiogenesis patterns in patient-derived organoids.Translational psychiatry · 2024Article
- Exploring autophagy-related prognostic genes of Alzheimer's disease based on pathway crosstalk analysis.Bosnian journal of basic medical sciences · 2022Article
- CD40L protects against mouse hepatitis virus-induced neuroinflammatory demyelination.PLoS pathogens · 2021Article
- Interactions of SARS-CoV-2 with the Blood-Brain Barrier.International journal of molecular sciences · 2021Review
- The regulatory function of mixed lineage kinase 3 in tumor and host immunity.Pharmacology & therapeutics · 2021Review
- Memantine can protect against inflammation-based cognitive decline in geriatric depression.Brain, behavior, & immunity - health · 2020Article
- Article
- Combination of HIV-1 and Diabetes Enhances Blood Brain Barrier Injury via Effects on Brain Endothelium and Pericytes.International journal of molecular sciences · 2020Article
- Avian Reticuloendotheliosis Viral Oncogene Related B Regulates Lymphatic Endothelial Cells during Vessel Maturation and Is Required for Lymphatic Vessel Function in Adult Mice.The American journal of pathology · 2019Article
- Recent Expansions on Cellular Models to Uncover the Scientific Barriers Towards Drug Development for Alzheimer's Disease.Cellular and molecular neurobiology · 2019Review
- Frontline Science: c-Myc regulates P-selectin glycoprotein ligand-1 expression in monocytes during HIV-1 infection.Journal of leukocyte biology · 2017Article
- Inhibition of CD40-TRAF6 interactions by the small molecule inhibitor 6877002 reduces neuroinflammation.Journal of neuroinflammation · 2017Article
- Article
- Th17-skewed immune response and cluster of differentiation 40 ligand expression in canine steroid-responsive meningitis-arteritis, a large animal model for neutrophilic meningitis.Journal of neuroinflammation · 2017Article
- Frog Virus 3 dissemination in the brain of tadpoles, but not in adult Xenopus, involves blood brain barrier dysfunction.Scientific reports · 2016Article
- Modeling HIV-1 Induced Neuroinflammation in Mice: Role of Platelets in Mediating Blood-Brain Barrier Dysfunction.PloS one · 2016Article
- Interferon gamma induces protective non-canonical signaling pathways in primary neurons.Journal of neurochemistry · 2015Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Human immunodeficiency virus 1 (HIV-1) infection may result in activation of peripheral monocytes followed by their infiltration into the CNS, where the release of proinflammatory mediators causes neurologic disease. Previously, we detected high levels of soluble CD40 ligand (CD40L) in CSF and plasma of HIV-infected patients with cognitive impairment. We now show that CD40, a receptor for CD40L, is highly expressed in brain endothelial cells of patients affected by HIV-1 encephalitis (HIVE), suggesting an important role for the CD40/CD40L dyad in regulating blood-brain barrier (BBB) functions. This concept was further supported by in vitro experiments. Exposure of primary human brain microvascular endothelial cells (BMVECs) to CD40L upregulated the expression of adhesion molecules intracellular adhesion molecule-1 and vascular cell adhesion molecule-1, which caused a fourfold increase in monocyte adhesion to BMVECs and stimulated migration across an in vitro BBB model. Investigations into the intracellular signaling pathways that govern these events revealed that cJUN-N-terminal kinase (JNK) is critical to CD40 activation in the BMVECs. CD40L induced activation of mixed-lineage-kinase-3 and JNK, leading to the subsequent activation of cJUN/AP-1 (activating-protein-1). JNK inhibition in the BMVECs prevented CD40L-mediated induction of adhesion molecules, monocyte adhesion, and transendothelial migration. These new findings support the concept that the CD40/CD40L dyad plays an important role in HIVE neuroinflammation.
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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.