ArticleThe Journal of biological chemistry2009
Selective activation of the p38 MAPK pathway by synthetic monophosphoryl lipid A.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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.
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Who cites it
48 citing papers in PubMed, 96 citations in OpenAlex.
- Abatement of acrylonitrile-induced gastric injury by 2-Methoxyestradiol through inhibition of TLR4/MYD88/phospho-p38 MAPK axis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Adjuvant activity of a small molecule TLR4 agonist discovered via structure-based virtual screening.Communications biology · 2025Article
- The balance between proinflammatory, "bad", and immunomodulatory, "good", lipopolysaccharide for understanding gut-derived systemic inflammation.Frontiers in immunology · 2025Review
- Flotillins affect LPS-induced TLR4 signaling by modulating the trafficking and abundance of CD14.Cellular and molecular life sciences : CMLS · 2024Article
- Physicochemical characterization of biological and synthetic forms of two lipid A-based TLR4 agonists.Heliyon · 2023Article
- New Glucosamine-Based TLR4 Agonists: Design, Synthesis, Mechanism of Action, and In Vivo Activity as Vaccine Adjuvants.Journal of medicinal chemistry · 2023Article
- Lactobacillus improves the effects of prednisone on autoimmune hepatitis via gut microbiota-mediated follicular helper T cells.Cell communication and signaling : CCS · 2022Article
- OX40 agonist stimulation increases and sustains humoral and cell-mediated responses to SARS-CoV-2 protein and saRNA vaccines.Frontiers in immunology · 2022Article
- Synthetic Glycolipids as Molecular Vaccine Adjuvants: Mechanism of Action in Human Cells and In Vivo Activity.Journal of medicinal chemistry · 2021Article
- Article
- Polysaccharide Isolated FromFrontiers in pharmacology · 2021Article
- Lipopolysaccharide Reverses Hepatic Stellate Cell Activation Through Modulation of cMyb, Small Mothers Against Decapentaplegic, and CCAAT/Enhancer-Binding Protein C/EBP Transcription Factors.Hepatology (Baltimore, Md.) · 2020Article
- The Expression of Adenosine A2B Receptor on Antigen-Presenting Cells Suppresses CD8Cancer immunology research · 2020Article
- Dissociation of TRIF bias and adjuvanticity.Vaccine · 2020Article
- Selection of adjuvants for vaccines targeting specific pathogens.Expert review of vaccines · 2019Review
- Paediatric obstructive sleep apnoea syndrome (OSAS) is associated with tonsil colonisation by Streptococcus pyogenes.Scientific reports · 2016Article
- Type I interferon signaling contributes to the bias that Toll-like receptor 4 exhibits for signaling mediated by the adaptor protein TRIF.Science signaling · 2014Article
- Contribution of TLR4 and MyD88 for adjuvant monophosphoryl lipid A (MPLA) activity in a DNA prime-protein boost HIV-1 vaccine.Vaccine · 2014Article
- Review
- Gene expression profiles identify both MyD88-independent and MyD88-dependent pathways involved in the maturation of dendritic cells mediated by heparan sulfate: a novel adjuvant.Human vaccines & immunotherapeutics · 2014Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
TLR4 stimulation by lipopolysaccharide can cause both MAL/MyD88- and TRAM/TRIF (Toll IL-1 receptor domain-containing adaptor-inducing IFNbeta)-dependent signaling events. Monophosphoryl lipid A (MPLA), a low toxicity derivative of endotoxic lipopolysaccharide, enhances antibody responses, T cell expansion, and recall responses against antigens without causing excessive inflammatory side effects. Previously, we proposed that TRIF-biased activation of TLR4 by MPLA is responsible for its reduced toxicity while retaining potent adjuvant effects. However, some TRIF-associated genes, such as MCP-1, are only weakly expressed, and some MyD88-associated inflammatory and anti-inflammatory cytokines, such as tumor necrosis factor alpha and interleukin-10, are strongly activated after MPLA stimulation despite weak NF-kappaB but strong IRF3 activation. We now report that synthetic derivatives of MPLA retained TRIF bias as compared with synthetic diphosphoryl lipid A, indicating a change in a single phosphoryl group is sufficient for TRIF-biased TLR4 stimulation. We extend our previous observations by showing that sMLA induces strong p38 MAPK but weak JNK activation, resulting in high IP-10 (interferon-inducible protein 10), tumor necrosis factor alpha, and interleukin-10 but low MCP-1 transcript levels. Results of this study identify a novel biochemical mechanism for regulation of sMLA-induced gene expression.
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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.