scholarly journals Induction of the gene encoding mucosal vascular addressin cell adhesion molecule 1 by tumor necrosis factor alpha is mediated by NF-kappa B proteins.

1995 ◽  
Vol 92 (8) ◽  
pp. 3561-3565 ◽  
Author(s):  
M. Takeuchi ◽  
V. R. Baichwal
Keyword(s):  
Cell Adhesion ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cell Adhesion Molecule ◽  
Nf Kappa B ◽  
Gene Encoding ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Cell Adhesion Molecule 1 ◽  
Necrosis Factor

scholarly journals Differential regulation of vascular cell adhesion molecule-1 gene transcription by tumor necrosis factor alpha and interleukin-1 alpha in dermal microvascular endothelial cells

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 211-217 ◽  
Author(s):  
J Gille ◽  
RA Swerlick ◽  
TJ Lawley ◽  
SW Caughman
Keyword(s):  
Tumor Necrosis ◽  
Cell Adhesion Molecule ◽  
Interleukin 1 ◽  
Tnf Alpha ◽  
Vascular Cell Adhesion ◽  
Nf Kappa B ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Cell Adhesion Molecule 1 ◽  
Necrosis Factor

Abstract As part of the inflammatory response, the localization of leukocytes depends to an important degree on cytokine-induced expression of vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells (EC). We have previously shown that VCAM-1 expression is induced on human umbilical vein EC (HUVEC) by both tumor necrosis factor alpha (TNF- alpha) and interleukin-1 alpha (IL-1 alpha), whereas on human dermal microvascular EC (HDMEC) only TNF alpha results in VCAM-1 expression. To explore molecular mechanisms responsible for these contrasting patterns of VCAM-1 induction in HUVEC versus HDMEC, we performed transcriptional activation studies with VCAM-1-based reporter constructs and in vitro binding assays using two adjacent NF-kappa B binding sequences of the VCAM-1 promoter as a DNA probe. Previous studies have established that these NF-kappa B motifs are required for cytokine-induced VCAM-1 transcription, and may further mediate cell- specific VCAM-1 gene activation by cytokines. The findings reported here demonstrate a significant HDMEC-specific attenuation of VCAM-1 gene transcription in response to IL-1 alpha, but not TNF alpha. An upstream VCAM-1 gene regulatory region distinct from the NF-kappa B sites appears to function as an IL-1 alpha-mediated transcriptional repressor within HDMEC. This repressor region conveys IL-1 alpha- dependent, but not TNF alpha-dependent, inhibition of transcription driven by a heterologous cytokine response element and promoter.

scholarly journals Differential regulation of vascular cell adhesion molecule-1 gene transcription by tumor necrosis factor alpha and interleukin-1 alpha in dermal microvascular endothelial cells

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 211-217 ◽  
Author(s):  
J Gille ◽  
RA Swerlick ◽  
TJ Lawley ◽  
SW Caughman
Keyword(s):  
Tumor Necrosis ◽  
Cell Adhesion Molecule ◽  
Interleukin 1 ◽  
Tnf Alpha ◽  
Vascular Cell Adhesion ◽  
Nf Kappa B ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Cell Adhesion Molecule 1 ◽  
Necrosis Factor

As part of the inflammatory response, the localization of leukocytes depends to an important degree on cytokine-induced expression of vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells (EC). We have previously shown that VCAM-1 expression is induced on human umbilical vein EC (HUVEC) by both tumor necrosis factor alpha (TNF- alpha) and interleukin-1 alpha (IL-1 alpha), whereas on human dermal microvascular EC (HDMEC) only TNF alpha results in VCAM-1 expression. To explore molecular mechanisms responsible for these contrasting patterns of VCAM-1 induction in HUVEC versus HDMEC, we performed transcriptional activation studies with VCAM-1-based reporter constructs and in vitro binding assays using two adjacent NF-kappa B binding sequences of the VCAM-1 promoter as a DNA probe. Previous studies have established that these NF-kappa B motifs are required for cytokine-induced VCAM-1 transcription, and may further mediate cell- specific VCAM-1 gene activation by cytokines. The findings reported here demonstrate a significant HDMEC-specific attenuation of VCAM-1 gene transcription in response to IL-1 alpha, but not TNF alpha. An upstream VCAM-1 gene regulatory region distinct from the NF-kappa B sites appears to function as an IL-1 alpha-mediated transcriptional repressor within HDMEC. This repressor region conveys IL-1 alpha- dependent, but not TNF alpha-dependent, inhibition of transcription driven by a heterologous cytokine response element and promoter.

scholarly journals Distinct mechanisms for regulation of the interleukin-8 gene involve synergism and cooperativity between C/EBP and NF-kappa B.

1993 ◽  
Vol 13 (11) ◽  
pp. 7191-7198 ◽  
Author(s):  
B Stein ◽  
A S Baldwin
Keyword(s):  
Gene Expression ◽  
Tumor Necrosis Factor ◽  
Binding Site ◽  
Tumor Necrosis ◽  
Interleukin 8 ◽  
Cooperative Binding ◽  
Nf Kappa B ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

The interleukin-8 promoter is transcriptionally activated by interleukin-1, tumor necrosis factor alpha, phorbol myristate acetate, or hepatitis B virus X protein through a sequence located between positions -91 and -71. This region contains an NF-kappa B-like and a C/EBP-like binding site. We show here that several members of the NF-kappa B family, including p65, p50, p52, and c-Rel, can bind to this region, confirming an authentic NF-kappa B binding site in the interleukin-8 promoter. Further, C/EBP binds only weakly to the interleukin-8 promoter site. Electrophoretic mobility shift assays with proteins overexpressed in COS cells and with nuclear extracts from tumor necrosis factor alpha-stimulated HeLa cells demonstrated a strong cooperative binding of C/EBP to its site when NF-kappa B is bound to its adjacent binding site. Transfection studies lead to a model that suggests a highly complex regulation of interleukin-8 gene expression at multiple levels: independent binding of C/EBP and NF-kappa B to their respective sites, cooperative binding of C/EBP and NF-kappa B to DNA, and positive synergistic activation through the C/EBP binding site and inhibition through the NF-kappa B binding site by combinations of C/EBP and NF-kappa B. Thus, the ultimate regulation of interleukin-8 gene expression depends on the ratio of cellular C/EBP and NF-kappa B.

scholarly journals Distinct mechanisms for regulation of the interleukin-8 gene involve synergism and cooperativity between C/EBP and NF-kappa B

1993 ◽  
Vol 13 (11) ◽  
pp. 7191-7198 ◽  
Author(s):  
B Stein ◽  
A S Baldwin
Keyword(s):  
Gene Expression ◽  
Tumor Necrosis Factor ◽  
Binding Site ◽  
Tumor Necrosis ◽  
Interleukin 8 ◽  
Cooperative Binding ◽  
Nf Kappa B ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

The interleukin-8 promoter is transcriptionally activated by interleukin-1, tumor necrosis factor alpha, phorbol myristate acetate, or hepatitis B virus X protein through a sequence located between positions -91 and -71. This region contains an NF-kappa B-like and a C/EBP-like binding site. We show here that several members of the NF-kappa B family, including p65, p50, p52, and c-Rel, can bind to this region, confirming an authentic NF-kappa B binding site in the interleukin-8 promoter. Further, C/EBP binds only weakly to the interleukin-8 promoter site. Electrophoretic mobility shift assays with proteins overexpressed in COS cells and with nuclear extracts from tumor necrosis factor alpha-stimulated HeLa cells demonstrated a strong cooperative binding of C/EBP to its site when NF-kappa B is bound to its adjacent binding site. Transfection studies lead to a model that suggests a highly complex regulation of interleukin-8 gene expression at multiple levels: independent binding of C/EBP and NF-kappa B to their respective sites, cooperative binding of C/EBP and NF-kappa B to DNA, and positive synergistic activation through the C/EBP binding site and inhibition through the NF-kappa B binding site by combinations of C/EBP and NF-kappa B. Thus, the ultimate regulation of interleukin-8 gene expression depends on the ratio of cellular C/EBP and NF-kappa B.

scholarly journals Regulation of tumor necrosis factor alpha transcription in macrophages: involvement of four kappa B-like motifs and of constitutive and inducible forms of NF-kappa B.

1990 ◽  
Vol 10 (4) ◽  
pp. 1498-1506 ◽  
Author(s):  
M A Collart ◽  
P Baeuerle ◽  
P Vassalli
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Nf Kappa B ◽  
Necrosis Factor Alpha ◽  
Protein Subunits ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Stimulation Of

This study characterizes the interaction of murine macrophage nuclear proteins with the tumor necrosis factor alpha (TNF-alpha) promoter. Gel retardation and methylation interference assays showed that stimulation of TNF-alpha gene transcription in peritoneal exudate macrophages was accompanied by induction of DNA-binding proteins that recognized with different affinities four elements related to the kappa B consensus motif and a Y-box motif. We suggest that the basal level of TNF-alpha expression in macrophages is due to the binding of a constitutive form of NF-kappa B, present at low levels in nuclei from resting thioglycolate exudate peritoneal macrophages, to some if not all of the kappa B motifs; we postulate that this constitutive form contains only the 50-kilodalton (kDa) DNA-binding protein subunits of NF-kappa B, not the 65-kDa protein subunits (P. Baeuerle and D. Baltimore, Genes Dev. 3:1689-1698, 1989). Agents such as glucocorticoids, which decrease TNF-alpha transcription, diminished the basal level of nuclear NF-kappa B. Stimulation of Stimulation of TNF-alpha transcription in macrophages by lipopolysaccharide, gamma interferon, or cycloheximide led to an increased content of nuclear NF-kappa B. This induced factor represents a different form of NF-kappa B, since it generated protein-DNA complexes of slower mobility; we propose that this induced form of NF-kappa B contains both the 50- and 65-kDa protein subunits, the latter ones being necessary to bind NF-kappa B to its cytoplasmic inhibitor in uninduced cells (Baeuerle and Baltimore, Genes Dev., 1989). In resting cells, this inducible form of NF-kappa B was indeed detectable in the cytosol after deoxycholate treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

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