ArticleThe Journal of biological chemistry2011
Neu1 sialidase and matrix metalloproteinase-9 cross-talk is essential for Toll-like receptor activation and cellular signaling.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Mammalian Neuraminidases in Immune-Mediated Diseases: Mucins and Beyond.Frontiers in immunology · 2022Pooled it
- Desialylation and sialidase secretion from monocytes and macrophages upon LPS activation.Frontiers in immunology · 2026Article
- Decoding sialidase: physiological roles, pathological pathways, and clinical opportunities.Frontiers in cellular and infection microbiology · 2026Review
- Elastin-derived extracellular matrix fragments drive aging through innate immune activation.Nature aging · 2025Article
- Associations of genetic proxies for non-steroidal anti-inflammatory drugs with increased kidney stone risk: a Mendelian randomization study.Inflammopharmacology · 2025Article
- An Alternative Mode of GPCR Transactivation: Activation of GPCRs by Adhesion GPCRs.International journal of molecular sciences · 2025Review
- Acute COVID-19 and LongCOVID syndrome - molecular implications for therapeutic strategies - review.Frontiers in immunology · 2025Review
- Article
- Sialic acid in the regulation of blood cell production, differentiation and turnover.Immunology · 2024Review
- Article
- Article
- Non-steroidal anti-inflammatory drug target gene associations with major depressive disorders: a Mendelian randomisation study integrating GWAS, eQTL and mQTL Data.The pharmacogenomics journal · 2023Article
- Novel Therapeutic Target Critical for SARS-CoV-2 Infectivity and Induction of the Cytokine Release Syndrome.Cells · 2023Article
- Neuraminidase 1 promotes renal fibrosis development in male mice.Nature communications · 2023Article
- Review
- Sialidase Inhibitors with Different Mechanisms.Journal of medicinal chemistry · 2022Review
- Review
- SialidaseWorld journal of oncology · 2022Article
- MMP9: A Tough Target for Targeted Therapy for Cancer.Cancers · 2022Review
- Sialic acid blockade in dendritic cells enhances CD8Cellular and molecular life sciences : CMLS · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
The signaling pathways of mammalian Toll-like receptors (TLRs) are well characterized, but the precise mechanism(s) by which TLRs are activated upon ligand binding remains poorly defined. Recently, we reported a novel membrane sialidase-controlling mechanism that depends on ligand binding to its TLR to induce mammalian neuraminidase-1 (Neu1) activity, to influence receptor desialylation, and subsequently to induce TLR receptor activation and the production of nitric oxide and proinflammatory cytokines in dendritic and macrophage cells. The α-2,3-sialyl residue of TLR was identified as the specific target for hydrolysis by Neu1. Here, we report a membrane signaling paradigm initiated by endotoxin lipopolysaccharide (LPS) binding to TLR4 to potentiate G protein-coupled receptor (GPCR) signaling via membrane Gα(i) subunit proteins and matrix metalloproteinase-9 (MMP9) activation to induce Neu1. Central to this process is that a Neu1-MMP9 complex is bound to TLR4 on the cell surface of naive macrophage cells. Specific inhibition of MMP9 and GPCR Gα(i)-signaling proteins blocks LPS-induced Neu1 activity and NFκB activation. Silencing MMP9 mRNA using lentivirus MMP9 shRNA transduction or siRNA transfection of macrophage cells and MMP9 knock-out primary macrophage cells significantly reduced Neu1 activity and NFκB activation associated with LPS-treated cells. These findings uncover a molecular organizational signaling platform of a novel Neu1 and MMP9 cross-talk in alliance with TLR4 on the cell surface that is essential for ligand activation of TLRs and subsequent cellular signaling.
Indexed as
Identifiers
What OpenQuestion holds
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.