Tumour necrosis factor receptor I (p55) is upregulated on endothelial cells by exposure to the tumour-derived cytokine endothelial monocyte- activating polypeptide II (EMAP-II)

Adam C. Berger, H. Richard Alexander, Peter C. Wu, Guangqing Tang, Michael F X Gnant, Arnold Mixon, Ewa S. Turner, Steven K. Libutti

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Endothelial monocyte activating polypeptide-II (EMAP-II) is an inflammatory cytokine known to have a role in neutrophil and macrophage chemotaxis and in apoptosis. It is a tumour-derived cytokine that sensitizes tumour vasculature to the effects of systemic TNF. In order to gain insight into the mechanism by which EMAP-II sensitizes vessels to TNF, we focused on its effects on TNF receptor expression. In human umbilical vein endothelial cells (HUVEC), TNF-R1 mRNA is increased four-fold following incubation with recombinant EMAP-II. Conditioned media from cell lines known to produce high levels of EMAP-II upregulated TNF-R1 but not TNF-R2 by up to twenty-fold compared to media controls and low expressing cell lines; this effect was blocked by anti-EMAP-II antibody. Recombinant EMAP-II upregulated TNF-R1 expression by approximately six-fold. Analysis of HUVEC lysates by ELISA showed increased expression of TNF-R1 within 2 h; TNF-R2 expression was unaffected by recombinant EMAP-II. Finally, immunohistochemistry of human melanomas in vivo showed that TNF-R1 staining is increased on the vessels of tumours known to express high levels of EMAP-II compared to low EMAP-II expressing tumours. These results suggest that EMAP-II upregulates TNF-R1 expression by endothelial cells both in vitro and in vivo. This induction of TNF-R1 expression may be the mechanism by which EMAP-II sensitizes tumour endothelium to the effects of TNF leading to haemorrhagic necrosis. (C)2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)992-1000
Number of pages9
JournalCytokine
Volume12
Issue number7
DOIs
StatePublished - Jul 2000
Externally publishedYes

Fingerprint

Tumor Necrosis Factor Receptors
Endothelial cells
Tumors
Endothelial Cells
Cytokines
Neoplasms
Receptors, Tumor Necrosis Factor, Type II
Human Umbilical Vein Endothelial Cells
small inducible cytokine subfamily E, member 1
Cells
Cell Line
Macrophages
Chemotaxis
Conditioned Culture Medium
Endothelium
Melanoma
Neutrophils
Necrosis
Up-Regulation
Enzyme-Linked Immunosorbent Assay

Keywords

  • Apoptosis
  • Cytokine receptors
  • EMAP-II
  • Endothelial cells
  • Tumour necrosis factor

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Immunology
  • Immunology and Allergy

Cite this

Tumour necrosis factor receptor I (p55) is upregulated on endothelial cells by exposure to the tumour-derived cytokine endothelial monocyte- activating polypeptide II (EMAP-II). / Berger, Adam C.; Richard Alexander, H.; Wu, Peter C.; Tang, Guangqing; Gnant, Michael F X; Mixon, Arnold; Turner, Ewa S.; Libutti, Steven K.

In: Cytokine, Vol. 12, No. 7, 07.2000, p. 992-1000.

Research output: Contribution to journalArticle

Berger, Adam C. ; Richard Alexander, H. ; Wu, Peter C. ; Tang, Guangqing ; Gnant, Michael F X ; Mixon, Arnold ; Turner, Ewa S. ; Libutti, Steven K. / Tumour necrosis factor receptor I (p55) is upregulated on endothelial cells by exposure to the tumour-derived cytokine endothelial monocyte- activating polypeptide II (EMAP-II). In: Cytokine. 2000 ; Vol. 12, No. 7. pp. 992-1000.
@article{32bdbc57dc9d41a9828ba34c5817d3e2,
title = "Tumour necrosis factor receptor I (p55) is upregulated on endothelial cells by exposure to the tumour-derived cytokine endothelial monocyte- activating polypeptide II (EMAP-II)",
abstract = "Endothelial monocyte activating polypeptide-II (EMAP-II) is an inflammatory cytokine known to have a role in neutrophil and macrophage chemotaxis and in apoptosis. It is a tumour-derived cytokine that sensitizes tumour vasculature to the effects of systemic TNF. In order to gain insight into the mechanism by which EMAP-II sensitizes vessels to TNF, we focused on its effects on TNF receptor expression. In human umbilical vein endothelial cells (HUVEC), TNF-R1 mRNA is increased four-fold following incubation with recombinant EMAP-II. Conditioned media from cell lines known to produce high levels of EMAP-II upregulated TNF-R1 but not TNF-R2 by up to twenty-fold compared to media controls and low expressing cell lines; this effect was blocked by anti-EMAP-II antibody. Recombinant EMAP-II upregulated TNF-R1 expression by approximately six-fold. Analysis of HUVEC lysates by ELISA showed increased expression of TNF-R1 within 2 h; TNF-R2 expression was unaffected by recombinant EMAP-II. Finally, immunohistochemistry of human melanomas in vivo showed that TNF-R1 staining is increased on the vessels of tumours known to express high levels of EMAP-II compared to low EMAP-II expressing tumours. These results suggest that EMAP-II upregulates TNF-R1 expression by endothelial cells both in vitro and in vivo. This induction of TNF-R1 expression may be the mechanism by which EMAP-II sensitizes tumour endothelium to the effects of TNF leading to haemorrhagic necrosis. (C)2000 Academic Press.",
keywords = "Apoptosis, Cytokine receptors, EMAP-II, Endothelial cells, Tumour necrosis factor",
author = "Berger, {Adam C.} and {Richard Alexander}, H. and Wu, {Peter C.} and Guangqing Tang and Gnant, {Michael F X} and Arnold Mixon and Turner, {Ewa S.} and Libutti, {Steven K.}",
year = "2000",
month = "7",
doi = "10.1006/cyto.2000.0687",
language = "English (US)",
volume = "12",
pages = "992--1000",
journal = "Cytokine",
issn = "1043-4666",
publisher = "Academic Press Inc.",
number = "7",

}

TY - JOUR

T1 - Tumour necrosis factor receptor I (p55) is upregulated on endothelial cells by exposure to the tumour-derived cytokine endothelial monocyte- activating polypeptide II (EMAP-II)

AU - Berger, Adam C.

AU - Richard Alexander, H.

AU - Wu, Peter C.

AU - Tang, Guangqing

AU - Gnant, Michael F X

AU - Mixon, Arnold

AU - Turner, Ewa S.

AU - Libutti, Steven K.

PY - 2000/7

Y1 - 2000/7

N2 - Endothelial monocyte activating polypeptide-II (EMAP-II) is an inflammatory cytokine known to have a role in neutrophil and macrophage chemotaxis and in apoptosis. It is a tumour-derived cytokine that sensitizes tumour vasculature to the effects of systemic TNF. In order to gain insight into the mechanism by which EMAP-II sensitizes vessels to TNF, we focused on its effects on TNF receptor expression. In human umbilical vein endothelial cells (HUVEC), TNF-R1 mRNA is increased four-fold following incubation with recombinant EMAP-II. Conditioned media from cell lines known to produce high levels of EMAP-II upregulated TNF-R1 but not TNF-R2 by up to twenty-fold compared to media controls and low expressing cell lines; this effect was blocked by anti-EMAP-II antibody. Recombinant EMAP-II upregulated TNF-R1 expression by approximately six-fold. Analysis of HUVEC lysates by ELISA showed increased expression of TNF-R1 within 2 h; TNF-R2 expression was unaffected by recombinant EMAP-II. Finally, immunohistochemistry of human melanomas in vivo showed that TNF-R1 staining is increased on the vessels of tumours known to express high levels of EMAP-II compared to low EMAP-II expressing tumours. These results suggest that EMAP-II upregulates TNF-R1 expression by endothelial cells both in vitro and in vivo. This induction of TNF-R1 expression may be the mechanism by which EMAP-II sensitizes tumour endothelium to the effects of TNF leading to haemorrhagic necrosis. (C)2000 Academic Press.

AB - Endothelial monocyte activating polypeptide-II (EMAP-II) is an inflammatory cytokine known to have a role in neutrophil and macrophage chemotaxis and in apoptosis. It is a tumour-derived cytokine that sensitizes tumour vasculature to the effects of systemic TNF. In order to gain insight into the mechanism by which EMAP-II sensitizes vessels to TNF, we focused on its effects on TNF receptor expression. In human umbilical vein endothelial cells (HUVEC), TNF-R1 mRNA is increased four-fold following incubation with recombinant EMAP-II. Conditioned media from cell lines known to produce high levels of EMAP-II upregulated TNF-R1 but not TNF-R2 by up to twenty-fold compared to media controls and low expressing cell lines; this effect was blocked by anti-EMAP-II antibody. Recombinant EMAP-II upregulated TNF-R1 expression by approximately six-fold. Analysis of HUVEC lysates by ELISA showed increased expression of TNF-R1 within 2 h; TNF-R2 expression was unaffected by recombinant EMAP-II. Finally, immunohistochemistry of human melanomas in vivo showed that TNF-R1 staining is increased on the vessels of tumours known to express high levels of EMAP-II compared to low EMAP-II expressing tumours. These results suggest that EMAP-II upregulates TNF-R1 expression by endothelial cells both in vitro and in vivo. This induction of TNF-R1 expression may be the mechanism by which EMAP-II sensitizes tumour endothelium to the effects of TNF leading to haemorrhagic necrosis. (C)2000 Academic Press.

KW - Apoptosis

KW - Cytokine receptors

KW - EMAP-II

KW - Endothelial cells

KW - Tumour necrosis factor

UR - http://www.scopus.com/inward/record.url?scp=0343962297&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0343962297&partnerID=8YFLogxK

U2 - 10.1006/cyto.2000.0687

DO - 10.1006/cyto.2000.0687

M3 - Article

C2 - 10880244

AN - SCOPUS:0343962297

VL - 12

SP - 992

EP - 1000

JO - Cytokine

JF - Cytokine

SN - 1043-4666

IS - 7

ER -