Suppression of endothelial cell activity by inhibition of TNFa

Shu Q, Amin MA, Ruth JH, Campbell PL, Koch AE.
Source: Arthritis Res Ther
Publication Date: (2012)
Issue: 14(2): R88
Research Area:
Basic Research
Cells used in publication:
Endothelial, MV lung, human (HMVEC-L)
Species: human
Tissue Origin: lung
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 tube formation on Matrigel (P < 0.05). CONCLUSION: Our data support the hypothesis that certolizumab pegol inhibits TNFa-dependent leukocyte adhesion and angiogenesis, probably via inhibition of angiogenic adhesion molecule expression and angiogenic chemokine secretion. Comment in Therapy: TNF inhibition suppresses angiogenic mechanisms implicated in RA. [Nat Rev Rheumatol. 2012]