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 language | English (US) |
|---|---|
| Pages (from-to) | 1699-1710 |
| Number of pages | 12 |
| Journal | Journal of Immunology |
| Volume | 172 |
| Issue number | 3 |
| State | Published - Feb 1 2004 |
| Externally published | Yes |
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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 journal › Article
}
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.
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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 -