suppression of endothelial cell activity by inhibition of tnfαtnfα抑制内皮细胞活性的抑制.pdf

Shu et al. Arthritis Research Therapy 2012, 14:R88 /content/14/2/R88 RESEARCH ARTICLE Open Access Suppression of endothelial cell activity by inhibition of TNFa 1,2 2 2 2 2,3* Qiang Shu , Mohammad A Amin , Jeffrey H Ruth , Phillip L Campbell and Alisa E Koch Abstract Introduction: TNFa is a proinflammatory cytokine that plays a central role in the pathogenesis of rheumatoid arthritis (RA). We investigated the effects of certolizumab pegol, a TNFa blocker, on endothelial cell function and angiogenesis. Methods: Human dermal microvascular endothelial cells (HMVECs) were stimulated with TNFa with or without certolizumab pegol. TNFa-induced adhesion molecule expression and angiogenic chemokine secretion were measured by cell surface ELISA and angiogenic chemokine ELISA, respectively. We also examined the effect of certolizumab pegol on TNFa-induced myeloid human promyelocytic leukemia (HL-60) cell adhesion to HMVECs, as well as blood vessels in RA synovial tissue using the Stamper-Woodruff assay. Lastly, we performed HMVEC chemotaxis, and tube formation. Results: Certolizumab pegol significantly blocked TNFa-induced HMVEC cell surface angiogenic E-selectin, vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression and angiogenic chemokine secretion (P 0.05). We found that certolizumab pegol significantly inhibited TNFa-induced HL-60 cell adhesion to HMVECs (P 0.05), and blocked HL-60 cell adhesion to RA synovial tissue vasculature (P 0.05). TNFa also enhanced HMVEC chemotaxis compared with the negative control group (P 0.05) and this chemotactic response was significantly reduced by certolizumab pegol (P 0.05). Certolizumab pegol inhibited TNFa-induced HMVEC