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

Virol J. 2007 Sep 14;4:87. doi: 10.1186/1743-422X-4-87.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cyclooxygenase 2 / biosynthesis*
  • Dinoprostone / biosynthesis
  • Endothelial Cells / cytology
  • Endothelial Cells / enzymology*
  • Endothelial Cells / virology*
  • Gene Expression Regulation*
  • Herpesvirus 8, Human / metabolism*
  • Humans
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics

Substances

  • G protein-coupled receptor, Human herpesvirus 8
  • Receptors, Chemokine
  • Recombinant Proteins
  • Cyclooxygenase 2
  • Dinoprostone