Kaposi's sarcoma-associated herpesvirus-G protein-coupled receptor-expressing endothelial cells exhibit reduced migration and stimulated chemotaxis by chemokine inverse agonists

Jean Pierre Couty, Monica Lupu-Meiri, Yoram Oron, Marvin C. Gershengorn

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

A constitutively active G protein-coupled receptor (GPCR) encoded by Kaposi's sarcoma-associated herpesvirus (human herpesvirus-8) (KSHV) is expressed in endothelial (spindle) cells of Kaposi's sarcoma lesions. In this study, we report novel effects of basal signaling by this receptor and of inverse agonist chemokines on migration of KSHV-GPCR-expressing mouse lung endothelial cells. We show that basal signaling by KSHV-GPCR inhibits migration of endothelial cells in two systems, movement through porous filters and in vitro wound closure. Naturally occurring chemokines, interferon γ-inducible protein-10 and stromal-derived factor-1, which act as inverse agonists at KSHV-GPCR, abrogate the inhibition of migration and stimulate directed migration (or chemotaxis) of these cells. Thus, the expression of KSHV-GPCR may allow infected endothelial cells in situ to remain in a localized environment or to directionally migrate along a gradient of specific chemokines that are inverse agonists at KSHV-GPCR.

Original languageEnglish
Pages (from-to)1142-1147
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume329
Issue number3
DOIs
StatePublished - Jun 2009

Funding

FundersFunder number
National Institute of Diabetes and Digestive and Kidney DiseasesZIADK011007

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