IFN-α Sensitizes Human Umbilical Vein Endothelial Cells to Apoptosis Induced by Double-Stranded RNA

William Kaiser, Jonathan L. Kaufman, Margaret K. Offermann

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

The ability of endothelial cells to mount an efficient antiviral response is important in restricting viral dissemination and eliminating viral infection from the endothelium and surrounding tissues. We demonstrate that dsRNA, a molecular signature of viral infection, induced apoptosis in HUVEC, and priming with IFN-α shortened the time between when dsRNA was encountered and when apoptosis was initiated. IFN-α priming induced higher levels of mRNA for dsRNA-activated protein kinase, 2′5′-oligoadenylate synthetase, and Toll-like receptor 3, transcripts that encode dsRNA-responsive proteins. dsRNA induced activation of dsRNA-activated protein kinase and nuclear translocation of transcription factors RelA and IFN regulatory factor-3 in IFN-α-primed HUVECs before the activation of intrinsic and extrinsic apoptotic pathways. These changes did not occur in the absence of dsRNA, and apoptosis resulting from incubation with dsRNA occurred much later when cells were not primed with IFN-α. The entire population of IFN-α-primed HUVECs underwent nuclear translocation of RelA and IFN regulatory factor-3 in response to dsRNA, whereas less than one-half of the population responded with apoptosis. When IFN-α-primed HUVECs were coincubated with dsRNA and proteasome inhibitors, all HUVECs were rendered susceptible to dsRNA-induced apoptosis. These studies provide evidence that many endothelial cells that are alerted to the risk of infection by IFN-α would undergo apoptosis sooner in response to dsRNA than non-IFN-α-primed cells, and this would enhance the likelihood of eliminating infected cells prior to the production of progeny virions.

Original languageEnglish (US)
Pages (from-to)1699-1710
Number of pages12
JournalJournal of Immunology
Volume172
Issue number3
StatePublished - Feb 1 2004
Externally publishedYes

Fingerprint

Double-Stranded RNA
Human Umbilical Vein Endothelial Cells
Apoptosis
Interferon Regulatory Factor-3
Virus Diseases
Protein Kinases
Transcription Factor RelA
Endothelial Cells
Toll-Like Receptor 3
Proteasome Inhibitors
Ligases
Virion
Population
Endothelium
Antiviral Agents
Messenger RNA
Infection
Proteins

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

IFN-α Sensitizes Human Umbilical Vein Endothelial Cells to Apoptosis Induced by Double-Stranded RNA. / Kaiser, William; Kaufman, Jonathan L.; Offermann, Margaret K.

In: Journal of Immunology, Vol. 172, No. 3, 01.02.2004, p. 1699-1710.

Research output: Contribution to journalArticle

Kaiser, William ; Kaufman, Jonathan L. ; Offermann, Margaret K. / IFN-α Sensitizes Human Umbilical Vein Endothelial Cells to Apoptosis Induced by Double-Stranded RNA. In: Journal of Immunology. 2004 ; Vol. 172, No. 3. pp. 1699-1710.
@article{82bc3e478e7c4fa0b8ff9553622c0525,
title = "IFN-α Sensitizes Human Umbilical Vein Endothelial Cells to Apoptosis Induced by Double-Stranded RNA",
abstract = "The ability of endothelial cells to mount an efficient antiviral response is important in restricting viral dissemination and eliminating viral infection from the endothelium and surrounding tissues. We demonstrate that dsRNA, a molecular signature of viral infection, induced apoptosis in HUVEC, and priming with IFN-α shortened the time between when dsRNA was encountered and when apoptosis was initiated. IFN-α priming induced higher levels of mRNA for dsRNA-activated protein kinase, 2′5′-oligoadenylate synthetase, and Toll-like receptor 3, transcripts that encode dsRNA-responsive proteins. dsRNA induced activation of dsRNA-activated protein kinase and nuclear translocation of transcription factors RelA and IFN regulatory factor-3 in IFN-α-primed HUVECs before the activation of intrinsic and extrinsic apoptotic pathways. These changes did not occur in the absence of dsRNA, and apoptosis resulting from incubation with dsRNA occurred much later when cells were not primed with IFN-α. The entire population of IFN-α-primed HUVECs underwent nuclear translocation of RelA and IFN regulatory factor-3 in response to dsRNA, whereas less than one-half of the population responded with apoptosis. When IFN-α-primed HUVECs were coincubated with dsRNA and proteasome inhibitors, all HUVECs were rendered susceptible to dsRNA-induced apoptosis. These studies provide evidence that many endothelial cells that are alerted to the risk of infection by IFN-α would undergo apoptosis sooner in response to dsRNA than non-IFN-α-primed cells, and this would enhance the likelihood of eliminating infected cells prior to the production of progeny virions.",
author = "William Kaiser and Kaufman, {Jonathan L.} and Offermann, {Margaret K.}",
year = "2004",
month = "2",
day = "1",
language = "English (US)",
volume = "172",
pages = "1699--1710",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - IFN-α Sensitizes Human Umbilical Vein Endothelial Cells to Apoptosis Induced by Double-Stranded RNA

AU - Kaiser, William

AU - Kaufman, Jonathan L.

AU - Offermann, Margaret K.

PY - 2004/2/1

Y1 - 2004/2/1

N2 - The ability of endothelial cells to mount an efficient antiviral response is important in restricting viral dissemination and eliminating viral infection from the endothelium and surrounding tissues. We demonstrate that dsRNA, a molecular signature of viral infection, induced apoptosis in HUVEC, and priming with IFN-α shortened the time between when dsRNA was encountered and when apoptosis was initiated. IFN-α priming induced higher levels of mRNA for dsRNA-activated protein kinase, 2′5′-oligoadenylate synthetase, and Toll-like receptor 3, transcripts that encode dsRNA-responsive proteins. dsRNA induced activation of dsRNA-activated protein kinase and nuclear translocation of transcription factors RelA and IFN regulatory factor-3 in IFN-α-primed HUVECs before the activation of intrinsic and extrinsic apoptotic pathways. These changes did not occur in the absence of dsRNA, and apoptosis resulting from incubation with dsRNA occurred much later when cells were not primed with IFN-α. The entire population of IFN-α-primed HUVECs underwent nuclear translocation of RelA and IFN regulatory factor-3 in response to dsRNA, whereas less than one-half of the population responded with apoptosis. When IFN-α-primed HUVECs were coincubated with dsRNA and proteasome inhibitors, all HUVECs were rendered susceptible to dsRNA-induced apoptosis. These studies provide evidence that many endothelial cells that are alerted to the risk of infection by IFN-α would undergo apoptosis sooner in response to dsRNA than non-IFN-α-primed cells, and this would enhance the likelihood of eliminating infected cells prior to the production of progeny virions.

AB - The ability of endothelial cells to mount an efficient antiviral response is important in restricting viral dissemination and eliminating viral infection from the endothelium and surrounding tissues. We demonstrate that dsRNA, a molecular signature of viral infection, induced apoptosis in HUVEC, and priming with IFN-α shortened the time between when dsRNA was encountered and when apoptosis was initiated. IFN-α priming induced higher levels of mRNA for dsRNA-activated protein kinase, 2′5′-oligoadenylate synthetase, and Toll-like receptor 3, transcripts that encode dsRNA-responsive proteins. dsRNA induced activation of dsRNA-activated protein kinase and nuclear translocation of transcription factors RelA and IFN regulatory factor-3 in IFN-α-primed HUVECs before the activation of intrinsic and extrinsic apoptotic pathways. These changes did not occur in the absence of dsRNA, and apoptosis resulting from incubation with dsRNA occurred much later when cells were not primed with IFN-α. The entire population of IFN-α-primed HUVECs underwent nuclear translocation of RelA and IFN regulatory factor-3 in response to dsRNA, whereas less than one-half of the population responded with apoptosis. When IFN-α-primed HUVECs were coincubated with dsRNA and proteasome inhibitors, all HUVECs were rendered susceptible to dsRNA-induced apoptosis. These studies provide evidence that many endothelial cells that are alerted to the risk of infection by IFN-α would undergo apoptosis sooner in response to dsRNA than non-IFN-α-primed cells, and this would enhance the likelihood of eliminating infected cells prior to the production of progeny virions.

UR - http://www.scopus.com/inward/record.url?scp=1642525760&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1642525760&partnerID=8YFLogxK

M3 - Article

C2 - 14734752

AN - SCOPUS:1642525760

VL - 172

SP - 1699

EP - 1710

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -