Small molecule antagonism of oxysterol-induced Epstein-Barr virus induced gene 2 (EBI2) activation.

Authors: Benned-Jensen T, Madsen CM, Arfelt KN, Smethurts C, Blanchard A, Jepras R, Rosenkilde MM.
Publisher/Year: FEBS Open Bio. 19;3:156-60.
Pub Med ID/Journal ID: PMID:23772388


The Epstein-Barr virus induced gene 2 (EBI2) was recently identified as the first oxysterol-activated 7TM receptor. EBI2 is essential for B cell trafficking within lymphoid tissues and thus the humoral immune response in general. Here we characterize the antagonism of the non-peptide molecule GSK682753A, which blocks oxysterol-induced G-protein activation, β-arrestin recruitment and B-cell chemotaxis. We furthermore demonstrate that activation triggers pertussis toxin-sensitive MAP kinase phosphorylation, which is also inhibited by GSK682753A. Thus, EBI2 signalling in B cells mediates key phenotypic functions via signalling pathways amenable to manipulation providing additional therapeutic options for inhibiting EBI2 activity.