ArticleJournal of leukocyte biology2012
The HIV-1 protease inhibitor nelfinavir activates PP2 and inhibits MAPK signaling in macrophages: a pathway to reduce inflammation.
Article in Journal of leukocyte biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Viral Induced Oxidative and Inflammatory Response in Alzheimer's Disease Pathogenesis with Identification of Potential Drug Candidates: A Systematic Review using Systems Biology Approach.Current neuropharmacology · 2019Pooled it
- Preventive and therapeutic benefits of nelfinavir in rhesus macaques and human beings infected with SARS-CoV-2.Signal transduction and targeted therapy · 2023Trial
- Increased inflammation but similar physical composition and function in older-aged, HIV-1 infected subjects.BMC immunology · 2015Trial
- Dabigatran Prevents Lipopolysaccharide-Mediated Apoptosis in Zebrafish Through a Thrombin-Independent Mechanism.Shock (Augusta, Ga.) · 2026Article
- Unlocking Novel Therapeutic Potential of Angiotensin II Receptor Blockers.International journal of molecular sciences · 2025Review
- Anti-atherogenic immune checkpoint TIM-3 as a promising pharmacologic target toward ischemic heart diseases: a prospective review.Molecular biology reports · 2025Review
- Drug target inference by mining transcriptional data using a novel graph convolutional network framework.Protein & cell · 2022Article
- The Impact of Matrix Metalloproteinase-9 on the Sequential Steps of the Metastatic Process.International journal of molecular sciences · 2020Review
- The Anti-Angiogenic Effects of Anti-Human Immunodeficiency Virus Drugs.Frontiers in oncology · 2020Review
- The HIV protease inhibitor darunavir prevents kidney injury via HIV-independent mechanisms.Scientific reports · 2019Article
- Article
- HIV-1 Infection Primes Macrophages Through STAT Signaling to Promote Enhanced Inflammation and Viral Replication.AIDS research and human retroviruses · 2017Article
- Tuning of AKT-pathway by Nef and its blockade by protease inhibitors results in limited recovery in latently HIV infected T-cell line.Scientific reports · 2016Article
- Δ(9)-Tetrahydrocannabinol treatment during human monocyte differentiation reduces macrophage susceptibility to HIV-1 infection.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2014Article
- Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The HIV-1 PI NFV has off-target effects upon host enzymes, including inhibition of the 20S proteasome, resulting in activation of PP1. HIV-1-associated monocyte/macrophage activation, in part a result of systemically elevated levels of microbial products including LPS, is associated with risk of mortality, independent of viremia or CD4 T cell loss. This study tested the hypothesis that activation of protein phosphatases by NFV would reduce activation of monocytes/macrophages through dephosphorylation of signal transduction proteins. NFV uniquely blocked LPS-induced production by human monocyte-derived macrophages of the inflammatory cytokines TNF and IL-6, as well as sCD14. Although NFV failed to modulate NF-κB, NFV treatment reduced phosphorylation of AKT and MAPKs. Inhibition of PP2 with okadaic acid blocked the anti-inflammatory effect of NFV, whereas the PP1 inhibitor calyculin A failed to counter the anti-inflammatory effects of NFV. For in vivo studies, plasma sCD14 and LPS were monitored in a cohort of 31 pediatric HIV-1 patients for over 2 years of therapy. Therapy, including NFV, reduced sCD14 levels significantly compared with IDV or RTV, independent of ΔLPS levels, VL, CD4 T cell frequency, or age. The hypothesis was supported as NFV induced activation of PP2 in macrophages, resulting in disruption of inflammatory cell signaling pathways. In vivo evidence supports that NFV may offer beneficial effects independent of antiviral activity by reducing severity of chronic innate immune activation in HIV-1 infection.
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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.