PMID- 9916692
OWN - NLM
STAT- MEDLINE
DCOM- 19990208
LR  - 20141125
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 162
IP  - 2
DP  - 1999 Jan 15
TI  - Nuclear factor-kappa B p65 mediates the assembly and activation of the 
      TNF-responsive element of the murine monocyte chemoattractant-1 gene.
PG  - 727-34
AB  - TNF-alpha transcriptionally regulates murine monocyte chemoattractant protein-1 
      (MCP-1) expression. Three approaches were used to determine the mechanism by 
      which TNF regulates MCP-1. Mutation analysis showed that two distal kappa B 
      sites, a novel dimethylsulfate-hypersensitive sequence, and a promoter proximal 
      SP-1 site were required for TNF induction. Although the kappa B sites and the 
      hypersensitive sequence function as a NF-kappa B-mediated enhancer, regulating 
      induction by TNF, stereospecific alignment of the kappa B sites was not critical. 
      Trans-activation studies conducted by cotransfection of p50 and/or p65 expression 
      vectors with MCP-1 constructions showed that TNF regulates MCP-1 through NF-kappa 
      B. Examination of MCP-1 induction in NF-kappa B-disrupted embryonic fibroblasts 
      showed that p65 was necessary for both the induction and the TNF-induced protein 
      occupancy of the enhancer in vivo. The action of the antioxidant inhibitor of 
      NF-kappa B activation, pyrrolidine dithiocarbamate, in wild-type and NF-kappa B 
      mutant cells was examined. The results suggested that TNF activates NF-kappa B 
      through both pyrrolidine dithiocarbamate-sensitive and -insensitive mechanisms. 
      This study illustrates the crucial role for NF-kappa B p65 in the induction of 
      the MCP-1 gene by TNF and in the assembly of a NF-kappa B dependent enhancer in 
      vivo.
FAU - Ping, D
AU  - Ping D
AD  - Department of Microbiology and Immunology, Emory University School of Medicine, 
      Emory University, Atlanta, GA 30322, USA.
FAU - Boekhoudt, G H
AU  - Boekhoudt GH
FAU - Rogers, E M
AU  - Rogers EM
FAU - Boss, J M
AU  - Boss JM
LA  - eng
GR  - CA74271/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antioxidants)
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (NF-kappa B p50 Subunit)
RN  - 0 (Protein Isoforms)
RN  - 0 (Pyrrolidines)
RN  - 0 (Thiocarbamates)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 25769-03-3 (pyrrolidine dithiocarbamic acid)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Antioxidants/pharmacology
MH  - Chemokine CCL2/biosynthesis/*genetics/metabolism
MH  - Enhancer Elements, Genetic/*immunology
MH  - Gene Expression Regulation/drug effects/*immunology
MH  - Humans
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - NF-kappa B/antagonists & inhibitors/deficiency/genetics/*physiology
MH  - NF-kappa B p50 Subunit
MH  - Protein Isoforms/antagonists & inhibitors
MH  - Pyrrolidines/pharmacology
MH  - Sequence Alignment
MH  - Thiocarbamates/pharmacology
MH  - Transcription Factor RelA
MH  - Tumor Necrosis Factor-alpha/*physiology
EDAT- 1999/01/23 00:00
MHDA- 1999/01/23 00:01
CRDT- 1999/01/23 00:00
PHST- 1999/01/23 00:00 [pubmed]
PHST- 1999/01/23 00:01 [medline]
PHST- 1999/01/23 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1999 Jan 15;162(2):727-34.