Suppression of endothelial cell activity by inhibition of tumor necrosis factor-alpha (Arthritis Research & Therapy)

IntroductionTumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine which plays a central role in the pathogenesis of rheumatoid arthritis (RA). We investigated the effects of certolizumab pegol, a TNF-alpha blocker, on endothelial cell (EC) function and angiogenesis. Methods: Human dermal microvascular endothelial cells (HMVECs) were stimulated with TNF-alpha with or without certolizumab pegol. TNF-alpha induced adhesion molecule expression and angiogenic chemokine secretion were measured by cell surface ELISA and ELISAs, respectively. We also examined the effect of certolizumab pegol on TNF-alpha induced myeloid human promyelocytic leukemia cell (HL-60) adhesion to HMVECs, as well as blood vessels in RA synovial tissue (ST) using the Stamper-Woodruff assay. Lastly, we performed HMVEC chemotaxis, and tube formation. Results: Certolizumab pegol significantly blocked TNF-alpha induced HMVEC cell surface angiogenic E-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1 expression and angiogenic chemokine secretion (P