ArticleThe Journal of biological chemistry2015
Microglial Heparan Sulfate Proteoglycans Facilitate the Cluster-of-Differentiation 14 (CD14)/Toll-like Receptor 4 (TLR4)-Dependent Inflammatory Response.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 64 citations in OpenAlex.
- Structural insights into glycan recognition by plant immune receptors: a comparative perspective with animal innate immune systems.The Plant journal : for cell and molecular biology · 2026Review
- Age-associated neuronal micronuclei formation and transfer to microglia.Frontiers in aging neuroscience · 2026Article
- Regulation of neutrophil function by the extracellular matrix.Biochemical Society transactions · 2025Review
- Lymphocyte-Activation Gene 3 Facilitates Pathological Tau Neuron-to-Neuron Transmission.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Neuronal Ndst1 depletion accelerates prion protein clearance and slows neurodegeneration in prion infection.PLoS pathogens · 2023Article
- Single-cell RNA sequencing identifies hippocampal microglial dysregulation in diet-induced obesity.iScience · 2023Article
- Proteoglycans and glycosaminoglycans in central nervous system injury.American journal of physiology. Cell physiology · 2022Review
- Sulfated Hyaluronan Binds to Heparanase and Blocks Its Enzymatic and Cellular Actions in Carcinoma Cells.International journal of molecular sciences · 2022Article
- Beta3Gn-T7 Is a Keratan Sulfate β1,3Frontiers in neuroanatomy · 2022Article
- Targeting the "sweet spot" in septic shock - A perspective on the endothelial glycocalyx regulating proteins Heparanase-1 and -2.Matrix biology plus · 2021Review
- Heparanase overexpression impedes perivascular clearance of amyloid-β from murine brain: relevance to Alzheimer's disease.Acta neuropathologica communications · 2021Article
- Mechanisms of Mitochondrial Dysfunction in Lysosomal Storage Disorders: A Review.Journal of clinical medicine · 2020Review
- Immunomodulatory Role of the Extracellular Matrix Within the Liver Disease Microenvironment.Frontiers in immunology · 2020Review
- Heparanase-2 protects from LPS-mediated endothelial injury by inhibiting TLR4 signalling.Scientific reports · 2019Article
- Systemic LPS-induced Aβ-solubilization and clearance in AβPP-transgenic mice is diminished by heparanase overexpression.Scientific reports · 2019Article
- Heparan Sulfate Proteoglycans as Relays of Neuroinflammation.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2018Review
- Danger-Associated Molecular Patterns Derived From the Extracellular Matrix Provide Temporal Control of Innate Immunity.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2018Review
- A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo.Nature biotechnology · 2018Article
- Understanding the Role of Innate Immunity in the Response to Intracortical Microelectrodes.Critical reviews in biomedical engineering · 2018Review
- TREM2-Ligand Interactions in Health and Disease.Journal of molecular biology · 2017Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Microglia rapidly mount an inflammatory response to pathogens in the central nervous system (CNS). Heparan sulfate proteoglycans (HSPGs) have been attributed various roles in inflammation. To elucidate the relevance of microglial HSPGs in a pro-inflammatory response we isolated microglia from mice overexpressing heparanase (Hpa-tg), the HS-degrading endoglucuronidase, and challenged them with lipopolysaccharide (LPS), a bacterial endotoxin. Prior to LPS-stimulation, the LPS-receptor cluster-of-differentiation 14 (CD14) and Toll-like receptor 4 (TLR4; essential for the LPS response) were similarly expressed in Ctrl and Hpa-tg microglia. However, compared with Ctrl microglia, Hpa-tg cells released significantly less tumor necrosis factor-α (TNFα), essentially failed to up-regulate interleukin-1β (IL1β) and did not initiate synthesis of proCD14. Isolated primary astroyctes expressed TLR4, but notably lacked CD14 and in contrast to microglia, LPS challenge induced a similar TNFα response in Ctrl and Hpa-tg astrocytes, while neither released IL1β. The astrocyte TNFα-induction was thus attributed to CD14-independent TLR4 activation and was unaffected by the cells HS status. Equally, the suppressed LPS-response in Hpa-tg microglia indicated a loss of CD14-dependent TLR4 activation, suggesting that microglial HSPGs facilitate this process. Indeed, confocal microscopy confirmed interactions between microglial HS and CD14 in LPS-stimulated microglia and a potential HS-binding motif in CD14 was identified. We conclude that microglial HSPGs facilitate CD14-dependent TLR4 activation and that heparanase can modulate this mechanism.
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