title: Suppression of endothelial cell activity by inhibition of TNFα.
abstract: BACKGROUND
  TNFα is a proinflammatory cytokine that plays a central role in the pathogenesis of rheumatoid arthritis (RA). We investigated the effects of certolizumab pegol, a TNFα blocker, on endothelial cell function and angiogenesis.
  
  
  METHODS
  Human dermal microvascular endothelial cells (HMVECs) were stimulated with TNFα with or without certolizumab pegol. TNFα-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 TNFα-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 TNFα-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 TNFα-induced HL-60 cell adhesion to HMVECs (P < 0.05), and blocked HL-60 cell adhesion to RA synovial tissue vasculature (P < 0.05). TNFα 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 TNFα-induced HMVEC tube formation on Matrigel (P < 0.05).
  
  
  CONCLUSIONS
  Our data support the hypothesis that certolizumab pegol inhibits TNFα-dependent leukocyte adhesion and angiogenesis, probably via inhibition of angiogenic adhesion molecule expression and angiogenic chemokine secretion.
authors.affiliation: Department of Internal Medicine, Qilu Hospital of Shandong University, 1107 Jinan Culture Road, Jinan City, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shu
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Amin
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Ruth
authors.forename: Phillip L
authors.initials: PL
authors.lastname: Campbell
authors.forename: Alisa E
authors.initials: AE
authors.lastname: Koch
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000502:physiology*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D000068582:Certolizumab Pegol; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D018922:HL-60 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000276:immunology; D011092:Polyethylene Glycols; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018925:Chemokines; D007140:Immunoglobulin Fab Fragments; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; D000068582:Certolizumab Pegol