Objectives: Previous studies have reported the presence of CD86 (B7.2) costimulatory molecule on endothelial cells (ECs) and recent data have shown that CTLA4-Ig (abatacept), used as a biological agent in rheumatoid arthritis, interacts with CD86 expressed on different cells involved in synovitis. Therefore, the effects of CTLA4-Ig/CD86 interaction on VEGFR-2 (vascular endothelial growth factor receptor 2) and ICAM1 expression, were evaluated in cultured ECs.
Methods: Activated ECs (γIFN 500 U/ml or IL-17 100 ng/ml), treated with CTLA4-Ig (10, 100, 500 μg/ml) were analysed for CD86, VEGFR-2 and ICAM1 expression, by flow cytometry (FACS), by western blot (WB) and quantitative real time PCR (qRT-PCR).
Results: Following CTLA4-Ig treatment (10, 100, 500 μg/ml; 24 hrs), activated ECs decreased their CD86-positivity at FACS: 66, 59, 51%, respectively, versus 68% of untreated cells (cnt) (for γIFN-activated cells) and 42, 47, 46% versus 71% (cnt) (for IL-17-activated ECs). Gamma-IFN-activated ECs, treated with CTLA4-Ig, showed a dose-dependent decrease only for ICAM1 fluorescence. Whereas, WB showed a significant decrease (p<0.05) for both ICAM1 and VEGFR-2 after CTLA4-Ig 500 μg/ml (3 and 24 hrs) and for VEGFR-2 also after CTLA4-Ig 100 μg/ml (3 hrs). QRT-PCR showed a significant decrease (p<0.05) for VEGFR-2 after CTLA4-Ig 500 μg/ml (3 and 24 hrs) and after CTLA4-Ig 100 μg/ml (limited at 3 hrs). QRT-PCR for ICAM1 was negative at 3 and 24 hrs, possibly since it was to late to be detected.
Conclusions: Results support a CTLA4-Ig/CD86 interaction on γIFN and IL-17 activated ECs modulation, in the expression of VEGFR-2 and ICAM1, both relevant for inflammatory and angiogenetic processes, suggesting ECs as a further target for abatacept.
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