PMID- 10486238
OWN - NLM
STAT- MEDLINE
DCOM- 19990929
LR  - 20071114
IS  - 0014-4800 (Print)
IS  - 0014-4800 (Linking)
VI  - 66
IP  - 3
DP  - 1999 Aug
TI  - Role of transcription factor NF-kappaB in asbestos-induced TNFalpha response from 
      macrophages.
PG  - 201-10
AB  - Asbestos exposure in humans is associated with inflammatory, fibrotic, and 
      malignant diseases in the lung. Increasing evidence supports the hypothesis that 
      the production of proinflammatory cytokines such as tumor necrosis factor-alpha 
      (TNFalpha) is an important mediator of the pathologic responses of asbestosis. In 
      this study, we examine the role of nuclear transcription factor-kappaB 
      (NF-kappaB) and free oxygen radicals in asbestos-induced TNFalpha gene and 
      protein expression in lung macrophages. Exposure of the cells to crocidolite 
      asbestos caused a parallel increase in TNFalpha production and NF-kappaB 
      activation, as analyzed by enzyme-linked immunosorbent assay and electrophoretic 
      mobility shift assay. Inhibition of NF-kappaB by SN50, an inhibitor of NF-kappaB 
      nuclear translocation, or by sequence-specific oligonucleotides directed against 
      the NF-kappaB binding site of TNFalpha promoter attenuated the asbestos effect on 
      TNFalpha production. Gene transfection assays using an expression plasmid 
      containing a luciferase reporter gene and a TNFalpha-derived NF-kappaB gene 
      promoter further indicated the dependence of NF-kappaB activation on 
      asbestos-induced gene expression. The effects of asbestos on NF-kappaB and 
      TNFalpha activation were inhibited by oxygen radical scavengers and were enhanced 
      by antioxidant enzyme inhibitors. These results indicate that asbestos-induced 
      TNFalpha gene expression is mediated through a process that involves NF-kappaB 
      activation and free radical reactions.
CI  - Copyright 1999 Academic Press.
FAU - Cheng, N
AU  - Cheng N
AD  - Department of Basic Pharmaceutical Sciences, West Virginia University, 
      Morgantown, West Virginia 26506, USA.
FAU - Shi, X
AU  - Shi X
FAU - Ye, J
AU  - Ye J
FAU - Castranova, V
AU  - Castranova V
FAU - Chen, F
AU  - Chen F
FAU - Leonard, S S
AU  - Leonard SS
FAU - Vallyathan, V
AU  - Vallyathan V
FAU - Rojanasakul, Y
AU  - Rojanasakul Y
LA  - eng
GR  - HL54291/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Exp Mol Pathol
JT  - Experimental and molecular pathology
JID - 0370711
RN  - 0 (Free Radical Scavengers)
RN  - 0 (NF-kappa B)
RN  - 0 (Peptides)
RN  - 0 (SN50 peptide)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 11062-77-4 (Superoxides)
RN  - 12001-28-4 (Asbestos, Crocidolite)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Animals
MH  - Asbestos, Crocidolite/*toxicity
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Free Radical Scavengers/pharmacology
MH  - Gene Expression/drug effects
MH  - Luciferases/analysis/biosynthesis/genetics/metabolism
MH  - Macrophages, Alveolar/*drug effects/metabolism
MH  - Male
MH  - NF-kappa B/antagonists & inhibitors/*metabolism
MH  - Peptides/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Superoxides/metabolism
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/*biosynthesis
EDAT- 1999/09/16 00:00
MHDA- 1999/09/16 00:01
CRDT- 1999/09/16 00:00
PHST- 1999/09/16 00:00 [pubmed]
PHST- 1999/09/16 00:01 [medline]
PHST- 1999/09/16 00:00 [entrez]
AID - S0014-4800(99)92268-2 [pii]
AID - 10.1006/exmp.1999.2268 [doi]
PST - ppublish
SO  - Exp Mol Pathol. 1999 Aug;66(3):201-10. doi: 10.1006/exmp.1999.2268.