Metal ions potentiate microglia responsiveness to endotoxin
| Autor: | B. Mary E. von Blomberg, Dessy Rachmawati, Rik J. Scheper, Hetty J. Bontkes, Daphne Y.S. Vogel, Inás W.A. Alsalem, Laura A. N. Peferoen, Sandra Amor, Ingrid M.W. van Hoogstraten |
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| Přispěvatelé: | Pathology, Amsterdam Neuroscience - Neuroinfection & -inflammation, Molecular cell biology and Immunology |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Male Lipopolysaccharide Immunology Stimulation Pharmacology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Immunology and Allergy Humans THP1 cell line Cells Cultured Aged Aged 80 and over Toll-like receptor Analysis of Variance Brain Diseases Innate immune system Microglia Dose-Response Relationship Drug Chemistry Interleukin-6 Interleukin-8 Neurotoxicity Brain Drug Synergism Middle Aged medicine.disease Flow Cytometry Endotoxins 030104 developmental biology medicine.anatomical_structure Neurology Biochemistry Metals TLR4 Female Neurology (clinical) 030217 neurology & neurosurgery |
| Zdroj: | Rachmawati, D, Peferoen, L A N, Vogel, D Y S, Alsalem, I W A, Amor, S, Bontkes, H J, von Blomberg, BME, Scheper, R J & van Hoogstraten, I M W 2016, ' Metal ions potentiate microglia responsiveness to endotoxin ', Journal of Neuroimmunology, vol. 291, pp. 89-95 . https://doi.org/10.1016/j.jneuroim.2015.12.013 Journal of Neuroimmunology, 291, 89-95. Elsevier |
| ISSN: | 1872-8421 0165-5728 |
| DOI: | 10.1016/j.jneuroim.2015.12.013 |
| Popis: | Oral metal exposure has been associated with diverse adverse reactions, including neurotoxicity. We showed previously that dentally applied metals activate dendritic cells (MoDC) via TLR4 (Ni, Co, Pd) and TLR3 (Au). It is still unknown whether the low levels of dental metals reaching the brain can trigger local innate cells or prime them to become more responsive. Here we tested whether dentally applied metals (Cr, Fe, Co, Ni, Cu, Zn, Au, Hg) activate primary human microglia in vitro and, as a model, monocytic THP-1-cells, in high non-toxic as well as near-physiological concentrations. In addition the effects of 'near-physiological' metal exposure on endotoxin (LPS) responsiveness of these cells were evaluated. IL-8 and IL-6 production after 24h was used as read out. In high, non-toxic concentrations all transition metals except Cr induced IL-8 and IL-6 production in microglia, with Ni and Co providing the strongest stimulation. When using near-physiological doses (up to 10× the normal plasma concentration), only Zn and Cu induced significant IL-8 production. Of note, the latter metals also markedly potentiated LPS responsiveness of microglia and THP-1 cells. In conclusion, transition metals activate microglia similar to MoDCs. In near-physiological concentrations Zn and Cu are the most effective mediators of innate immune activation. A clear synergism between innate responses to Zn/Cu and LPS was observed, shedding new light on the possible relation between oral metal exposure and neurotoxicity. |
| Databáze: | OpenAIRE |
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