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Evaluation of four α-diketones for toll-like receptor-4 (TLR-4) activation in a human transfected cell line.
- Source :
-
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association [Food Chem Toxicol] 2014 Dec; Vol. 74, pp. 117-9. Date of Electronic Publication: 2014 Oct 02. - Publication Year :
- 2014
-
Abstract
- Toll-like receptor-4 (TLR-4) activity is upregulated in persons with fibrotic lung diseases secondary to chronic inflammatory conditions like Crohn's disease and rheumatoid arthritis. We hypothesized that α-diketones associated with fixed obstructive lung disease may activate TLR-4. We utilized a human embryonic kidney cell assay (HEK293) with human TLR-4 receptors to test for potential activation effects of 2,3-butandeione, 2,3-pentanedione, 2,3-hexanedione, and 2,3-heptanedione at test concentrations of 1, 10, 100, and 1000 µM. The assay detects NF-κB-induced expression of secreted alkaline phosphatase measured after 16 h incubation by a UV-VIS Spectrometer at 650 nm. Escherichia coli K12 lipopolysaccharide (LPS) at 0.5 ng/mL served as a positive control and was added with each test compound to evaluate combined effects. None of the tested α-diketones were found to exhibit cytotoxicity, agonism, or synergistic effects with LPS in the human TLR-4 assay up to 1000 µM. Screening of 2,3-butanedione for agonist activity using the HEK assay with mouse TLR-4 receptors exhibited cytotoxicity at 1000 µM, but no agonist activity. We conclude that the tested α-diketones at relatively high concentrations in vitro do not exhibit TLR-4 agonist or synergistic activity and, therefore, apparently do not directly induce inflammasome activation through this pathway in humans or mice.<br /> (Copyright © 2014 Elsevier Ltd. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1873-6351
- Volume :
- 74
- Database :
- MEDLINE
- Journal :
- Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
- Publication Type :
- Academic Journal
- Accession number :
- 25280922
- Full Text :
- https://doi.org/10.1016/j.fct.2014.09.010