Classical and Alternative Activation of Rat Microglia Treated with Ultrapure Porphyromonas gingivalis Lipopolysaccharide In Vitro
| Autor: | Mary L Hall, Evan Czerwonka, Joshua Mayer, Alejandro M. S. Mayer, Lucas C Klemm, Zylfi Memedovski, Jin Han, Margaret Luce |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Lipopolysaccharides
Chemokine Lipopolysaccharide Health Toxicology and Mutagenesis CCL3 microglia lcsh:Medicine Toxicology Porphyromonas gingivalis Article Microbiology neuroinflammation 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Superoxides medicine Escherichia coli Animals Macrophage inflammatory protein periodontitis Neuroinflammation Cells Cultured 030304 developmental biology 0303 health sciences biology Microglia Chemistry lipopolysaccharide lcsh:R biology.organism_classification Rats Thromboxane B2 Oxidative Stress medicine.anatomical_structure Phenotype Matrix Metalloproteinase 9 biology.protein Cytokines Tumor necrosis factor alpha Inflammation Mediators 030217 neurology & neurosurgery |
| Zdroj: | Toxins, Vol 12, Iss 333, p 333 (2020) Toxins Volume 12 Issue 5 |
| ISSN: | 2072-6651 |
| Popis: | The possible relationship between periodontal disease resulting from the infection of gingival tissue by the Gram-negative bacterium Porphyromonas gingivalis (P. gingivalis) and the development of neuroinflammation remains under investigation. Recently, P. gingivalis lipopolysaccharide (LPS) was reported in the human brain, thus suggesting it might activate brain microglia, a cell type participating in neuroinflammation. We tested the hypothesis of whether in vitro exposure to ultrapure P. gingivalis LPS may result in classical and alternative activation phenotypes of rat microglia, with the concomitant release of cytokines and chemokines, as well as superoxide anion (O2&minus ), thromboxane B2 (TXB2), and matrix metalloprotease-9 (MMP-9). After an 18-h exposure of microglia to P. gingivalis LPS, the concentration-dependent responses were the following: 0.1&ndash 100 ng/mL P. gingivalis LPS increased O2&minus generation, with reduced inflammatory mediator generation 1000&ndash 10,000 ng/mL P. gingivalis LPS generated MMP-9, macrophage inflammatory protein 1&alpha (MIP-1&alpha /CCL3), macrophage inflammatory protein-2 (MIP-2/CXCL2) release and significant O2&minus generation 100,000 ng/mL P. gingivalis LPS sustained O2&minus production, maintained MMP-9, tumor necrosis factor-&alpha (TNF-&alpha ), and interleukin-6 (IL-6) release, and triggered elevated levels of MIP-1&alpha /CCL3, MIP-2/CXCL2, and cytokine-induced neutrophil chemoattractant 1 (CINC-1/CXCL-1), with a very low release of lactic dehydrogenase (LDH). Although P. gingivalis LPS was less potent than Escherichia coli (E. coli) LPS in stimulating TXB2, MMP-9, IL-6 and interleukin 10 (IL-10) generation, we observed that it appeared more efficacious in enhancing the release of O2&minus TNF-&alpha MIP-1&alpha /CCL3, MIP-2/CXCL2 and CINC-1/CXCL-1. Our results provide support to our research hypothesis because an 18-h in vitro stimulation with ultrapure P. gingivalis LPS resulted in the classical and alternative activation of rat brain microglia and the concomitant release of cytokines and chemokines. |
| Databáze: | OpenAIRE |
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