Kaposi's sarcoma associated herpesvirus G-protein coupled receptor activation of cyclooxygenase-2 in vascular endothelial cells

Bryan D. Shelby, Heather L. LaMarca, Harris E. McFerrin, Anne B. Nelson, Joseph A. Lasky, Gang Sun, Leslie Myatt, Margaret K. Offermann, Cindy A. Morris, Deborah E. Sullivan

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background. Kaposi's sarcoma associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS), a highly vascularized neoplasm characterized by endothelial-derived spindle-shaped tumor cells. KSHV-infected microvascular endothelial cells demonstrate increased cyclooxygenase-2 (COX-2) expression and KS lesions have high levels of prostaglandin E2(PGE2), a short-lived eicosanoid dependent on cyclooxygenase activity that has been linked to pathogenesis of other neoplasias. To determine whether increased COX-2 expression and PGE2 production is mediated by the angiogenic and tumorigenic KSHV-encoded G-protein coupled receptor (vGPCR), we developed a recombinant retrovirus to express vGPCR in Human Umbilical Vascular Endothelial Cells (HUVEC). Results. In the present study, we show that vGPCR-expressing HUVEC exhibit a spindle-like morphology that is characteristic of KS endothelial cells and demonstrate selective induction of PGE2 and COX-2. By treating vGPCR-expressing HUVEC with selective and non-selective COX inhibitors, we show that vGPCR-induced PGE2 production is dependent on the expression of COX-2 but not COX-1. Conclusion. Taken together, these results demonstrate that vGPCR induces expression of COX-2 and PGE2 that may mediate the paracrine effects of this key viral protein in KS pathogenesis.

Original languageEnglish (US)
Article number87
JournalVirology Journal
Volume4
DOIs
StatePublished - 2007
Externally publishedYes

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Human Herpesvirus 8
Cyclooxygenase 2
G-Protein-Coupled Receptors
Dinoprostone
Kaposi's Sarcoma
Umbilicus
Endothelial Cells
Prostaglandin-Endoperoxide Synthases
Neoplasms
Eicosanoids
Viral Proteins
Retroviridae

ASJC Scopus subject areas

  • Virology
  • Genetics(clinical)

Cite this

Shelby, B. D., LaMarca, H. L., McFerrin, H. E., Nelson, A. B., Lasky, J. A., Sun, G., ... Sullivan, D. E. (2007). Kaposi's sarcoma associated herpesvirus G-protein coupled receptor activation of cyclooxygenase-2 in vascular endothelial cells. Virology Journal, 4, [87]. https://doi.org/10.1186/1743-422X-4-87

Kaposi's sarcoma associated herpesvirus G-protein coupled receptor activation of cyclooxygenase-2 in vascular endothelial cells. / Shelby, Bryan D.; LaMarca, Heather L.; McFerrin, Harris E.; Nelson, Anne B.; Lasky, Joseph A.; Sun, Gang; Myatt, Leslie; Offermann, Margaret K.; Morris, Cindy A.; Sullivan, Deborah E.

In: Virology Journal, Vol. 4, 87, 2007.

Research output: Contribution to journalArticle

Shelby, BD, LaMarca, HL, McFerrin, HE, Nelson, AB, Lasky, JA, Sun, G, Myatt, L, Offermann, MK, Morris, CA & Sullivan, DE 2007, 'Kaposi's sarcoma associated herpesvirus G-protein coupled receptor activation of cyclooxygenase-2 in vascular endothelial cells', Virology Journal, vol. 4, 87. https://doi.org/10.1186/1743-422X-4-87
Shelby, Bryan D. ; LaMarca, Heather L. ; McFerrin, Harris E. ; Nelson, Anne B. ; Lasky, Joseph A. ; Sun, Gang ; Myatt, Leslie ; Offermann, Margaret K. ; Morris, Cindy A. ; Sullivan, Deborah E. / Kaposi's sarcoma associated herpesvirus G-protein coupled receptor activation of cyclooxygenase-2 in vascular endothelial cells. In: Virology Journal. 2007 ; Vol. 4.
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AB - Background. Kaposi's sarcoma associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS), a highly vascularized neoplasm characterized by endothelial-derived spindle-shaped tumor cells. KSHV-infected microvascular endothelial cells demonstrate increased cyclooxygenase-2 (COX-2) expression and KS lesions have high levels of prostaglandin E2(PGE2), a short-lived eicosanoid dependent on cyclooxygenase activity that has been linked to pathogenesis of other neoplasias. To determine whether increased COX-2 expression and PGE2 production is mediated by the angiogenic and tumorigenic KSHV-encoded G-protein coupled receptor (vGPCR), we developed a recombinant retrovirus to express vGPCR in Human Umbilical Vascular Endothelial Cells (HUVEC). Results. In the present study, we show that vGPCR-expressing HUVEC exhibit a spindle-like morphology that is characteristic of KS endothelial cells and demonstrate selective induction of PGE2 and COX-2. By treating vGPCR-expressing HUVEC with selective and non-selective COX inhibitors, we show that vGPCR-induced PGE2 production is dependent on the expression of COX-2 but not COX-1. Conclusion. Taken together, these results demonstrate that vGPCR induces expression of COX-2 and PGE2 that may mediate the paracrine effects of this key viral protein in KS pathogenesis.

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