ArticlePloS one2015
MD-2 determinants of nickel and cobalt-mediated activation of human TLR4.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 49 citations in OpenAlex.
- Metalloimmunotherapies: metal-driven regulatory networks in the immune microenvironment.Frontiers in immunology · 2026Review
- Adopting orphan receptors: zebrafish Tlr4 homologs mediate responses to group IX/X transition metals.Frontiers in immunology · 2025Article
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- Copper regulates the host innate immune response against bacterial infection via activation of ALPK1 kinase.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Sensitive detection of lipopolysaccharides by monitoring of interleukin-10 secretion from human PBMCs.microPublication biology · 2023Article
- Pro-Inflammatory Signalling PRRopels Cisplatin-Induced Toxicity.International journal of molecular sciences · 2022Review
- Toll-like receptor 4 is activated by platinum and contributes to cisplatin-induced ototoxicity.EMBO reports · 2021Article
- Update of the risk assessment of nickel in food and drinking water.EFSA journal. European Food Safety Authority · 2020Article
- An immunoinformatic approach driven by experimental proteomics: in silico design of a subunit candidate vaccine targeting secretory proteins of Leishmania donovani amastigotes.Parasites & vectors · 2020Article
- Upregulation of microRNA-4417 and Its Target Genes Contribute to Nickel Chloride-promoted Lung Epithelial Cell Fibrogenesis and Tumorigenesis.Scientific reports · 2017Article
- Effect of cobalt-mediated Toll-like receptor 4 activation on inflammatory responses in endothelial cells.Oncotarget · 2016Article
- Low-Coherence Reflectometry for Refractive Index Measurements of Cells in Micro-Capillaries.Sensors (Basel, Switzerland) · 2016Article
- Article
- Critical residues involved in Toll-like receptor 4 activation by cationic lipid nanocarriers are not located at the lipopolysaccharide-binding interface.Cellular and molecular life sciences : CMLS · 2015Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Recent findings unexpectedly revealed that human TLR4 can be directly activated by nickel ions. This activation is due to the coordination of nickel by a cluster of histidine residues on the ectodomain of human TLR4, which is absent in most other species. We aimed to elucidate the role of MD-2 in the molecular mechanism of TLR4/MD-2 activation by nickel, as nickel binding site on TLR4 is remote from MD-2, which directly binds the endotoxin as the main pathological activator of TLR4. We identified MD-2 and TLR4 mutants which abolished TLR4/MD-2 receptor activation by endotoxin but could nevertheless be significantly activated by nickel, which acts in synergy with LPS. Human TLR4/MD-2 was also activated by cobalt ions, while copper and cadmium were toxic in the tested concentration range. Activation of TLR4 by cobalt required MD-2 and was abolished by human TLR4 mutations of histidine residues at positions 456 and 458. We demonstrated that activation of TLR4 by nickel and cobalt ions can trigger both the MyD88-dependent and the -independent pathway. Based on our results we propose that predominantly hydrophobic interactions between MD-2 and TLR4 contribute to the stabilization of the TLR4/MD-2/metal ion complex in a conformation that enables activation.
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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.