PMID- 25280922
OWN - NLM
STAT- MEDLINE
DCOM- 20150803
LR  - 20141201
IS  - 1873-6351 (Electronic)
IS  - 0278-6915 (Linking)
VI  - 74
DP  - 2014 Dec
TI  - Evaluation of four alpha-diketones for toll-like receptor-4 (TLR-4) activation in a 
      human transfected cell line.
PG  - 117-9
LID - S0278-6915(14)00411-6 [pii]
LID - 10.1016/j.fct.2014.09.010 [doi]
AB  - 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 alpha-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 microM. The assay 
      detects NF-kappaB-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 
      alpha-diketones were found to exhibit cytotoxicity, agonism, or synergistic effects 
      with LPS in the human TLR-4 assay up to 1000 microM. Screening of 2,3-butanedione for 
      agonist activity using the HEK assay with mouse TLR-4 receptors exhibited 
      cytotoxicity at 1000 microM, but no agonist activity. We conclude that the tested 
      alpha-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.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - Kerger, Brent D
AU  - Kerger BD
AD  - Cardno ChemRisk, 130 Vantis, Suite 170, Aliso Viejo, CA 92656, USA. Electronic 
      address: brent.kerger@cardno.com.
FAU - Thuett, Kerry A
AU  - Thuett KA
AD  - Cardno ChemRisk, 101 2nd St. Suite 700, San Francisco, CA 94105, USA.
FAU - Finley, Brent L
AU  - Finley BL
AD  - Cardno ChemRisk, 231 Front St. Suite 201, Brooklyn, NY 11201, USA.
LA  - eng
PT  - Journal Article
DEP - 20141002
PL  - England
TA  - Food Chem Toxicol
JT  - Food and chemical toxicology : an international journal published for the British 
      Industrial Biological Research Association
JID - 8207483
RN  - 0 (Hexanones)
RN  - 0 (Ketones)
RN  - 0 (Pentanones)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 559ANR3NVS (2,3-hexanedione)
RN  - K324J5K4HM (Diacetyl)
RN  - K4WBE45SCM (2,3-pentanedione)
SB  - IM
MH  - Diacetyl/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - HEK293 Cells/drug effects
MH  - Hexanones/*pharmacology
MH  - Humans
MH  - Ketones/*pharmacology
MH  - Pentanones/*pharmacology
MH  - Toll-Like Receptor 4/antagonists & inhibitors/*drug effects
MH  - Up-Regulation/drug effects
OTO - NOTNLM
OT  - Bronchiolitis obliterans
OT  - Diacetyl
OT  - Fibrotic lung disease
OT  - Humans
OT  - Inflammasome
EDAT- 2014/10/05 06:00
MHDA- 2015/08/04 06:00
CRDT- 2014/10/05 06:00
PHST- 2014/06/14 00:00 [received]
PHST- 2014/09/18 00:00 [revised]
PHST- 2014/09/22 00:00 [accepted]
PHST- 2014/10/05 06:00 [entrez]
PHST- 2014/10/05 06:00 [pubmed]
PHST- 2015/08/04 06:00 [medline]
AID - S0278-6915(14)00411-6 [pii]
AID - 10.1016/j.fct.2014.09.010 [doi]
PST - ppublish
SO  - Food Chem Toxicol. 2014 Dec;74:117-9. doi: 10.1016/j.fct.2014.09.010. Epub 2014 
      Oct 2.