IL-6 in human cytomegalovirus secretome promotes angiogenesis and survival of endothelial cells through the stimulation of survivin

Sara Botto, Daniel Streblow, Victor De Filippis, Laura White, Craig N. Kreklywich, Patricia P. Smith, Patrizia Caposio

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Human cytomegalovirus (HCMV) is linked to the acceleration of vascular diseases such as atherosclerosis and transplant vasculopathy. One of the hallmarks of these diseases is angiogenesis (AG) and neovessel formation. Endothelial cells (ECs) are an integral part of AG and are sites of HCMV persistence. AG requires multiple synchronous processes that include EC proliferation, migration, and vessel stabilization. Virus-free supernatant (secretome) from HCMV-infected ECs induces AG. To identify factor(s) involved in this process, we performed a human cytokine array. Several cytokines were significantly induced in the HCMV secretomes including interleukin-6 (IL-6), granulocyte macrophage colony-stimulating factor, and IL-8/CXCL8. Using in vitroAG assays, neutralization of IL-6 significantly reduced neovessel formation. Addition of the HCMV secretome to preformed vessels extended neovessel survival, but this effect was blocked by neutralization of IL-6. In these cells, IL-6 prevented apoptosis by blocking caspase-3 and -7 activation through the induction of survivin. Neutralization of IL-6 receptor on ECs abolished the ability of HCMV secretome to increase survivin expression and activated effector caspases. Moreover, survivin shRNA expression induced rapid regression of tubule capillary networks in ECs stimulated with HCMV secretome and activated effector caspases. These observations may explain how CMV accelerates vascular disease despite limited infection in tissues.

Original languageEnglish (US)
Pages (from-to)352-361
Number of pages10
JournalBlood
Volume117
Issue number1
DOIs
StatePublished - Jan 6 2011

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Endothelial cells
Cytomegalovirus
Interleukin-6
Endothelial Cells
Effector Caspases
Cytokines
Interleukin-6 Receptors
Vascular Diseases
Transplants
Cell proliferation
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-8
Viruses
Caspase 3
Small Interfering RNA
Assays
Caspase 7
Stabilization
Chemical activation
Tissue

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

IL-6 in human cytomegalovirus secretome promotes angiogenesis and survival of endothelial cells through the stimulation of survivin. / Botto, Sara; Streblow, Daniel; De Filippis, Victor; White, Laura; Kreklywich, Craig N.; Smith, Patricia P.; Caposio, Patrizia.

In: Blood, Vol. 117, No. 1, 06.01.2011, p. 352-361.

Research output: Contribution to journalArticle

Botto, Sara ; Streblow, Daniel ; De Filippis, Victor ; White, Laura ; Kreklywich, Craig N. ; Smith, Patricia P. ; Caposio, Patrizia. / IL-6 in human cytomegalovirus secretome promotes angiogenesis and survival of endothelial cells through the stimulation of survivin. In: Blood. 2011 ; Vol. 117, No. 1. pp. 352-361.
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