ArticleJournal of neuroimmunology2008
HIV-1-infected and/or immune-activated macrophages regulate astrocyte CXCL8 production through IL-1beta and TNF-alpha: involvement of mitogen-activated protein kinases and protein kinase R.
Article in Journal of neuroimmunology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 58 citations in OpenAlex.
- Neuropathogenesis of HIV and emerging therapeutic targets.Expert opinion on therapeutic targets · 2022Review
- HIV-1 persistence in the CNS: Mechanisms of latency, pathogenesis and an update on eradication strategies.Virus research · 2021Review
- Exocytosis in Astrocytes.Biomolecules · 2021Review
- Co-receptor signaling in the pathogenesis of neuroHIV.Retrovirology · 2021Review
- Altered expression of fractalkine in HIV-1-infected astrocytes and consequences for the virus-related neurotoxicity.Journal of neurovirology · 2021Article
- HIV-Associated Neurotoxicity: The Interplay of Host and Viral Proteins.Mediators of inflammation · 2021Review
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- New Challenges of HIV-1 Infection: How HIV-1 Attacks and Resides in the Central Nervous System.Cells · 2019Review
- Linked CSF reduction of phosphorylated tau and IL-8 in HIV associated neurocognitive disorder.Scientific reports · 2019Article
- Reaching for the Stars in the Brain: Polymer-Mediated Gene Delivery to Human Astrocytes.Molecular therapy. Nucleic acids · 2018Article
- Zika virus propagation and release in human fetal astrocytes can be suppressed by neutral sphingomyelinase-2 inhibitor GW4869.Cell discovery · 2018Article
- Article
- Destination Brain: the Past, Present, and Future of Therapeutic Gene Delivery.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2017Review
- Classical Swine Fever Virus Infection and Its NS4A Protein Expression Induce IL-8 Production through MAVS Signaling Pathway in Swine Umbilical Vein Endothelial Cells.Frontiers in microbiology · 2017Article
- Neuropharmacologic Approaches to Restore the Brain's Microenvironment.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2016Review
- Strategies to target non-T-cell HIV reservoirs.Current opinion in HIV and AIDS · 2016Review
- Control of autoimmune CNS inflammation by astrocytes.Seminars in immunopathology · 2015Review
- Differential signaling mechanism for HIV-1 Nef-mediated production of IL-6 and IL-8 in human astrocytes.Scientific reports · 2015Article
- Leucine-rich repeat kinase 2 modulates neuroinflammation and neurotoxicity in models of human immunodeficiency virus 1-associated neurocognitive disorders.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Monocyte infiltration is an important pathogenic event in human immunodeficiency virus type one (HIV-1) associated dementia (HAD). CXCL8 (Interleukin 8, IL-8), a CXC chemokine that elicits chemotaxis of neutrophils, has recently been found to recruit monocytes or synergistically enhance CCL2-mediated monocyte migration. In this report, we demonstrate CXCL8 levels in the cerebrospinal fluid of HAD patients are higher than HIV-1 seropositive patients without neurological impairment. The underlying mechanisms regulating CXCL8 production during disease are not completely understood. We investigated the role of HIV-1-infected and immune-competent macrophages, the principal target cell and mediator of neuronal injury in HAD, in regulating astrocyte CXCL8 production. Immune-activated and HIV-1-infected human monocyte-derived-macrophages (MDM) conditioned media (MCM) induced production of CXCL8 by human astrocytes. This CXCL8 production was dependent on MDM IL-1beta and TNF-alpha production following viral and immune activation. CXCL8 production was reduced by inhibitors for mitogen-activated protein kinases (MAPKs), including p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinases (ERK1/2). Moreover, prolonged IL-1beta or TNF-alpha treatment activated double-stranded RNA-activated protein kinase (PKR). Inhibition of PKR prevented elevated CXCL8 production in astrocytes. We conclude that IL-1beta and TNF-alpha, produced from HIV-1-infected and immune-competent macrophages, are critical in astrocyte CXCL8 production. Multiple protein kinases, including p38, JNK, ERK1/2, and PKR, participate in the inflammatory response of astrocytes. These observations will help to identify effective therapeutic strategies to reduce high-levels of CXCL8-mediated CNS inflammation during HAD.
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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.