ArticleCells2021
Phosphorylation of Microglial IRF5 and IRF4 by IRAK4 Regulates Inflammatory Responses to Ischemia.
Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- ROR2 preserves alveolar bone homeostasis by orchestrating IRAK4-dependent suppression of CXCL8-driven osteolysis.Cell communication and signaling : CCS · 2026Article
- Escape of Kdm6a from X Chromosome Is Detrimental to Ischemic Brains via IRF5 Signaling.Translational stroke research · 2025Article
- Jianpi Yifei Tongluo recipe attenuates inflammation by promoting the expression of interferon regulatory factor 4 in the rat model of chronic obstructive pulmonary disease.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
- Blood-Brain Barrier-Penetrating Nanocarriers Enable Microglial-Specific Drug Delivery in Hypothalamic Neuroinflammation.Advanced healthcare materials · 2025Article
- Uncovering selection pressures on the IRF gene family in bats' immune system.Immunogenetics · 2025Article
- Interferon regulatory factor 5: a potential target for therapeutic intervention in inflammatory diseases.Frontiers in immunology · 2025Review
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
- ABBV-744 alleviates LPS-induced neuroinflammation via regulation of BATF2-IRF4-STAT1/3/5 axis.Acta pharmacologica Sinica · 2024Article
- Escape of Kdm6a from X chromosome is detrimental to ischemic brains via IRF5 signaling.Research square · 2024Article
- Central IRF4/5 Signaling Are Critical for Microglial Activation and Impact on Stroke Outcomes.Translational stroke research · 2024Article
- Lyn-mediated glycolysis enhancement of microglia contributes to neuropathic pain through facilitating IRF5 nuclear translocation in spinal dorsal horn.Journal of cellular and molecular medicine · 2023Article
- Emerging Targets for Modulation of Immune Response and Inflammation in Stroke.Neurochemical research · 2023Review
- A Markov random field model-based approach for differentially expressed gene detection from single-cell RNA-seq data.Briefings in bioinformatics · 2022Article
- Article
- Effects of adenovirus-mediated knockdown of IRAK4 on synovitis in the osteoarthritis rabbit model.Arthritis research & therapy · 2021Article
- Age and sex differences in primary microglia culture: A comparative study.Journal of neuroscience methods · 2021Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundInterferon Regulatory Factor (IRF) 5 and 4 play a determinant role in regulating microglial pro- and anti-inflammatory responses to cerebral ischemia. How microglial IRF5 and IRF4 signaling are activated has been elusive. We hypothesized that interleukin-1 receptor associated kinase 4 (IRAK4) phosphorylates and activates IRF5 and IRF4 in ischemic microglia. We aimed to explore the upstream signals of the two IRFs, and to determine how the IRAK4-IRF signaling regulates the expression of inflammatory mediators, and impacts neuropathology.
methodsSpontaneously Immortalized Murine (SIM)-A9 microglial cell line, primary microglia and neurons from C57BL/6 WT mice were cultured and exposed to oxygen-glucose deprivation (OGD), followed by stimulation with LPS or IL-4. An IRAK4 inhibitor (ND2158) was used to examine IRAK4's effects on the phosphorylation of IRF5/IRF4 and the impacts on neuronal morphology by co-immunoprecipitation (Co-IP)/Western blot, ELISA, and immunofluorescence assays.
resultsWe confirmed that IRAK4 formed a Myddosome with MyD88/IRF5/IRF4, and phosphorylated both IRFs, which subsequently translocated into the nucleus. Inhibition of IRAK4 phosphorylation quenched microglial pro-inflammatory response primarily, and increased neuronal viability and neurite lengths after ischemia.
conclusionsIRAK4 signaling is critical for microglial inflammatory responses and a potential therapeutic target for neuroinflammatory diseases including cerebral ischemia.
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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.