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


CONCLUSIONS
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.
Shelby
Bryan D
BD
Department of Microbiology and Immunology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA. bshelby@emory.edu
LaMarca
Heather L
HL
McFerrin
Harris E
HE
Nelson
Anne B
AB
Lasky
Joseph A
JA
Sun
Gang
G
Myatt
Leslie
L
Offermann
Margaret K
MK
Morris
Cindy A
CA
Sullivan
Deborah E
DE
D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis; D042783:Endothelial Cells / Q000166:cytology / Q000201:enzymology* / Q000821:virology*; D005786:Gene Expression Regulation; D019288:Herpesvirus 8, Human / Q000378:metabolism*; D006801:Humans; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics
C115448:G protein-coupled receptor, Human herpesvirus 8; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D051546:Cyclooxygenase 2; D015232:Dinoprostone