ArticlePloS one2011
Ibudilast, a pharmacologic phosphodiesterase inhibitor, prevents human immunodeficiency virus-1 Tat-mediated activation of microglial cells.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02714036 (A Multi-Center, Open-Label Biomarker Study to Evaluate MN-166 in Subjects With Amyotrophic Literal Sclerosis), which is not on this map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Multi-Center, Open-Label Biomarker Study to Evaluate MN-166 in Subjects With Amyotrophic Literal Sclerosis (ALS)
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Progress in Pathological and Therapeutic Research of HIV-Related Neuropathic Pain.Cellular and molecular neurobiology · 2023Pooled it
- Ibudilast and dipyridamole ameliorate murine γ-herpesvirus 68-induced acute hepatitis following airway infection.Virus genes · 2026Article
- Comprehensive analysis of spinal cord inflammatory factors in HIV Tat-induced neuropathy in mice.Neuroscience · 2026Article
- Emerging Potential of the Phosphodiesterase (PDE) Inhibitor Ibudilast for Neurodegenerative Diseases: An Update on Preclinical and Clinical Evidence.Molecules (Basel, Switzerland) · 2022Review
- Article
- Review
- A comprehensive study to delineate the role of an extracellular vesicle-associated microRNA-29a in chronic methamphetamine use disorder.Journal of extracellular vesicles · 2021Article
- Ibudilast Attenuates Folic Acid-Induced Acute Kidney Injury by Blocking Pyroptosis Through TLR4-Mediated NF-κB and MAPK Signaling Pathways.Frontiers in pharmacology · 2021Article
- Following spinal cord injury, PDE4B drives an acute, local inflammatory response and a chronic, systemic response exacerbated by gut dysbiosis and endotoxemia.Neurobiology of disease · 2019Article
- Article
- Role of microglia in methamphetamine-induced neurotoxicity.International journal of physiology, pathophysiology and pharmacology · 2017Review
- Ibudilast reverses the decrease in the synaptic signaling protein phosphatidylethanolamine-binding protein 1 (PEBP1) produced by chronic methamphetamine intake in rats.Drug and alcohol dependence · 2015Article
- Investigating the role of ankyrin-rich membrane spanning protein in human immunodeficiency virus type-1 Tat-induced microglia activation.Journal of neurovirology · 2015Article
- The cross-talk of HIV-1 Tat and methamphetamine in HIV-associated neurocognitive disorders.Frontiers in microbiology · 2015Review
- Platelet Activation in Human Immunodeficiency Virus Type-1 Patients Is Not Altered with Cocaine Abuse.PloS one · 2015Article
- Ibudilast (AV411), and its AV1013 analog, reduce HIV-1 replication and neuronal death induced by HIV-1 and morphine.AIDS (London, England) · 2014Article
- Interactions of HIV and drugs of abuse: the importance of glia, neural progenitors, and host genetic factors.International review of neurobiology · 2014Review
- Roles and functions of HIV-1 Tat protein in the CNS: an overview.Virology journal · 2013Review
- Targeting platelet-derived soluble CD40 ligand: a new treatment strategy for HIV-associated neuroinflammation?Journal of neuroinflammation · 2013Review
- Discovery, synthesis, and characterization of an orally bioavailable, brain penetrant inhibitor of mixed lineage kinase 3.Journal of medicinal chemistry · 2013Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Human Immunodeficiency Virus-1 (HIV-1)-associated neurocognitive disorders (HAND) occur, in part, due to the inflammatory response to viral proteins, such as the HIV-1 transactivator of transcription (Tat), in the central nervous system (CNS). Given the need for novel adjunctive therapies for HAND, we hypothesized that ibudilast would inhibit Tat-induced excess production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNFα) in microglial cells. Ibudilast is a non-selective cyclic AMP phosphodiesterase inhibitor that has recently shown promise as a treatment for neuropathic pain via its ability to attenuate glial cell activation. Accordingly, here we demonstrate that pre-treatment of both human and mouse microglial cells with increasing doses of ibudilast inhibited Tat-induced synthesis of TNFα by microglial cells in a manner dependent on serine/threonine protein phosphatase activity. Ibudilast had no effect on Tat-induced p38 MAP kinase activation, and blockade of adenosine A(2A) receptor activation did not reverse ibudilast's inhibition of Tat-induced TNFα production. Interestingly, ibudilast reduced Tat-mediated transcription of TNFα, via modulation of nuclear factor-kappa B (NF-κB) signaling, as shown by transcriptional activity of NF-κB and analysis of inhibitor of kappa B alpha (IκBα) stability. Together, our findings shed light on the mechanism of ibudilast's inhibition of Tat-induced TNFα production in microglial cells and may implicate ibudilast as a potential novel adjunctive therapy for the management of HAND.
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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.