ArticleInternational journal of molecular sciences2022
Modulation of Inflammatory Cytokine Production in Human Monocytes by cGMP and IRAK3.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Analysis of Phosphodiesterase-5 (PDE5) Inhibitors in Modulating Inflammatory Markers in Humans: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2025Pooled it
- IRAK signaling in cancers: mechanisms, targeting, and clinical implications.Expert opinion on investigational drugs · 2025Review
- Metabolic Reprogramming in Response to Freund's Adjuvants: Insights from Serum Metabolomics.Microorganisms · 2025Article
- Acute COVID-19 and LongCOVID syndrome - molecular implications for therapeutic strategies - review.Frontiers in immunology · 2025Review
- Interleukin-1 Receptor-Associated Kinase-3 Aggravates Neuroinflammatory Injury After Intracerebral Hemorrhage via Activation NF-κB/IL-17A Pathway in Mice.Journal of inflammation research · 2025Article
- Understanding chronic inflammation: couplings between cytokines, ROS, NO, CaFrontiers in immunology · 2025Review
- Exploring the biological functions and immune regulatory roles of IRAK3, TNFRSF1A, CX3CR1, and JUNB in T2DM combined with MAFLD: integrated bioinformatics and single-cell analysis.Frontiers in immunology · 2025Article
- Exploring of bladder cancer immune-related genes and potential therapeutic targets based on transcriptomic data and Mendelian randomization analysis.Frontiers in immunology · 2025Article
- Evaluation of effectiveness of bacteriophage purification methods.Virology journal · 2024Article
- Moonlighting Crypto-Enzymes and Domains as Ancient and Versatile Signaling Devices.International journal of molecular sciences · 2024Review
- Article
- Deciphering the molecular classification of pediatric sepsis: integrating WGCNA and machine learning-based classification with immune signatures for the development of an advanced diagnostic model.Frontiers in genetics · 2024Article
- Rethinking of phosphodiesterase 5 inhibition: the old, the new and the perspective in human health.Frontiers in endocrinology · 2024Review
- IRAK3 Knockout and Wildtype THP-1 Monocytes as Models for Endotoxin Detection Assays andInternational journal of molecular sciences · 2023Article
- Mutations in the Vicinity of the IRAK3 Guanylate Cyclase Center Impact Its Subcellular Localization and Ability to Modulate Inflammatory Signaling in Immortalized Cell Lines.International journal of molecular sciences · 2023Article
- Amino acid motifs for the identification of novel protein interactants.Computational and structural biotechnology journal · 2023Review
- The discovery of hidden guanylate cyclases (GCs) in theComputational and structural biotechnology journal · 2023Article
- Effects ofViruses · 2022Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Interleukin-1 receptor-associated kinase-3 (IRAK3) is a critical checkpoint molecule of inflammatory responses in the innate immune system. The pseudokinase domain of IRAK3 contains a guanylate cyclase (GC) centre that generates small amounts of cyclic guanosine monophosphate (cGMP) associated with IRAK3 functions in inflammation. However, the mechanisms of IRAK3 actions are poorly understood. The effects of low cGMP levels on inflammation are unknown, therefore a dose-response effect of cGMP on inflammatory markers was assessed in THP-1 monocytes challenged with lipopolysaccharide (LPS). Sub-nanomolar concentrations of membrane permeable 8-Br-cGMP reduced LPS-induced NFκB activity, IL-6 and TNF-α cytokine levels. Pharmacologically upregulating cellular cGMP levels using a nitric oxide donor reduced cytokine secretion. Downregulating cellular cGMP using a soluble GC inhibitor increased cytokine levels. Knocking down IRAK3 in THP-1 cells revealed that unlike the wild type cells, 8-Br-cGMP did not suppress inflammatory responses. Complementation of IRAK3 knockdown cells with wild type IRAK3 suppressed cytokine production while complementation with an IRAK3 mutant at GC centre only partially restored this function. Together these findings indicate low levels of cGMP form a critical component in suppressing cytokine production and in mediating IRAK3 action, and this may be via a cGMP enriched nanodomain formed by IRAK3 itself.
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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.