PMID- 11312646
OWN - NLM
STAT- MEDLINE
DCOM- 20010531
LR  - 20081121
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 172
IP  - 3
DP  - 2001 May 1
TI  - Propanil inhibits tumor necrosis factor-alpha production by reducing nuclear 
      levels of the transcription factor nuclear factor-kappab in the macrophage cell 
      line ic-21.
PG  - 186-93
AB  - Tumor necrosis factor-alpha (TNF-alpha) is an essential proinflammatory cytokine 
      whose production is normally stimulated by bacterial cell wall components, such 
      as lipopolysaccharide (LPS), during an infection. Macrophages stimulated with LPS 
      in vitro produce several cytokines, including TNF-alpha. LPS-stimulated primary 
      mouse macrophages produced less TNF-alpha protein and message after treatment 
      with the herbicide propanil (Xie et al., Toxicol. Appl. Pharmacol. 145, 184-191, 
      1997). Nuclear factor-kappaB (NF-kappaB) tightly regulates TNF-alpha 
      transcription. Therefore, as a step toward understanding the mechanism of the 
      effect of propanil on TNF-alpha transcription, IC-21 cells were transfected with 
      a TNF-alpha promoter-luciferase construct, and the effect of propanil on 
      luciferase activity was measured. Cells transfected with promoter constructs 
      containing a kappaB site showed decreased luciferase activity relative to 
      controls after propanil treatment. These observations implicated NF-kappaB 
      binding as an intracellular target of propanil. Further studies demonstrated a 
      marked reduction in the nuclear levels of the stimulatory p65 subunit of 
      NF-kappaB after propanil treatment, as measured by fluorescence confocal 
      microscopy and Western blot analysis. The p50 subunit of NF-kappaB was not found 
      to be reduced after propanil exposure by Western blot. Electrophoretic mobility 
      gel shift assays showed decreased DNA binding of both p65/p50 heterodimers and 
      p50/p50 homodimers to the kappaB3 site of the TNF-alpha promoter of 
      propanil-treated cells. The marked reduction in nuclear p65/p50 NF-kappaB levels 
      and diminished binding to the TNF-alpha promoter in propanil-treated cells are 
      consistent with reduced TNF-alpha levels induced by LPS.
CI  - Copyright 2001 Academic Press.
FAU - Frost, L L
AU  - Frost LL
AD  - Department of Microbiology and Immunology, West Virginia University, Morgantown, 
      West Virginia, 26506, USA.
FAU - Neeley, Y X
AU  - Neeley YX
FAU - Schafer, R
AU  - Schafer R
FAU - Gibson, L F
AU  - Gibson LF
FAU - Barnett, J B
AU  - Barnett JB
LA  - eng
GR  - ES07512/ES/NIEHS NIH HHS/United States
GR  - HL56888/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Herbicides)
RN  - 0 (NF-kappa B)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 709-98-8 (Propanil)
RN  - 9007-49-2 (DNA)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Blotting, Western
MH  - Cell Line
MH  - Cell Nucleus/*drug effects/metabolism
MH  - DNA/metabolism
MH  - Dimerization
MH  - Electrophoresis
MH  - Herbicides/*pharmacology
MH  - Luciferases/genetics
MH  - Macrophages/*drug effects/metabolism/ultrastructure
MH  - Mice
MH  - Microscopy, Confocal
MH  - NF-kappa B/chemistry/*metabolism
MH  - Promoter Regions, Genetic
MH  - Propanil/*pharmacology
MH  - Recombinant Fusion Proteins
MH  - Transcription, Genetic/drug effects
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/*biosynthesis/genetics
EDAT- 2001/04/21 10:00
MHDA- 2001/06/02 10:01
CRDT- 2001/04/21 10:00
PHST- 2001/04/21 10:00 [pubmed]
PHST- 2001/06/02 10:01 [medline]
PHST- 2001/04/21 10:00 [entrez]
AID - S0041-008X(01)99153-7 [pii]
AID - 10.1006/taap.2001.9153 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2001 May 1;172(3):186-93. doi: 10.1006/taap.2001.9153.