ArticleScientific reports2015
Annexin A2 binds to endosomes and negatively regulates TLR4-triggered inflammatory responses via the TRAM-TRIF pathway.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 90 citations in OpenAlex.
- The role of Annexin A2 in Alzheimer's disease: From cellular functions to therapeutic potential.The FEBS journal · 2026Review
- ANXA2 suppresses antiviral immunity by impeding STING Golgi translocation and disrupting the TBK1/IKKε-IRF3 axis.Journal of virology · 2026Article
- Annexin A2 negatively regulates IFN-β production through targeting the RLR signaling pathway.Journal of virology · 2026Article
- Targeting Annexin A2 to reactivate tumor-associated antigens presentation and relieve immune tolerance in liver cancer.Journal for immunotherapy of cancer · 2025Article
- Mapping Small Extracellular Vesicle Secretion Potential in Healthy Human Gingiva Using Spatial Transcriptomics.Current issues in molecular biology · 2025Article
- CRISPR screens with trastuzumab emtansine in HER2-positive breast cancer cell lines reveal new insights into drug resistance.Breast cancer research : BCR · 2025Article
- Annexin A: Cell Death, Inflammation, and Translational Medicine.Journal of inflammation research · 2025Review
- Annexin A1 and A2 in inflammatory bowel disease pathogenesis: exploring new avenues for diagnosis and treatment.Frontiers in immunology · 2025Review
- TLR-4: a promising target for chemotherapy-induced peripheral neuropathy.Molecular biology reports · 2024Review
- Pangolin scales as adaptations for innate immunity against pathogens.BMC biology · 2024Article
- Annexin A2: A Double-Edged Sword in Pathogen Infection.Pathogens (Basel, Switzerland) · 2024Review
- Multi-Omics Profiling Identifies Microglial Annexin A2 as a Key Mediator of NF-κB Pro-inflammatory Signaling in Ischemic Reperfusion Injury.Molecular & cellular proteomics : MCP · 2024Article
- Interplay of Extracellular Vesicles and TLR4 Signaling in Hepatocellular Carcinoma Pathophysiology and Therapeutics.Pharmaceutics · 2023Review
- Lymph node sharing between pancreas, gut, and liver leads to immune crosstalk and regulation of pancreatic autoimmunity.Immunity · 2023Article
- Inflammatory and tolerogenic myeloid cells determine outcome following human allergen challenge.The Journal of experimental medicine · 2023Article
- A C-type lectin induces NLRP3 inflammasome activation via TLR4 interaction in human peripheral blood mononuclear cells.Cellular and molecular life sciences : CMLS · 2023Article
- Differential Protein Expression ofPathogens (Basel, Switzerland) · 2023Article
- A functional variant of CD40 modulates clearance of hepatitis B virus in hepatocytes via regulation of the ANXA2/CD40/BST2 axis.Human molecular genetics · 2023Article
- Pseudorabies Virus Regulates the Extracellular Translocation of Annexin A2 To Promote Its Proliferation.Journal of virology · 2023Article
- Recombinant IL-37 Exerts an Anti-inflammatory Effect on Human Aortic Valve Interstitial Cells through Extracellular and Intracellular Actions.International journal of biological sciences · 2023Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Lipopolysaccharide (LPS) derived from Gram-negative bacteria activates plasma membrane signaling via Toll-like receptor 4 (TLR4) on host cells and triggers innate inflammatory responses, but the underlying mechanisms remain to be fully elucidated. Here we reveal a role for annexin A2 (AnxA2) in host defense against infection as anxa2(-/-) mice were highly susceptible to Gram-negative bacteria-induced sepsis with enhanced inflammatory responses. Computing analysis and biochemical experiments identified that constitutive AnxA2 expression facilitated TLR4 internalization and its subsequent translocation into early endosomal membranes. It activated the TRAM-dependent endosomal signaling, leading to the release of anti-inflammatory cytokines. Importantly, AnxA2 deficiency prolonged TLR4-mediated signaling from the plasma membrane, which was attributable to pro-inflammatory cytokine production (IL-6, TNFα and IL-1β). Thus, AnxA2 directly exerted negative regulation of inflammatory responses through TLR4-initiated TRAM-TRIF pathway occurring on endosomes. This study reveals AnxA2 as a critical regulator in infection-initiated inflammation, which protects the host from excessive inflammatory damage.
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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.