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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 2/2012

Open Access 01-04-2012 | Research article

Suppression of endothelial cell activity by inhibition of TNFα

Authors: Qiang Shu, Mohammad A Amin, Jeffrey H Ruth, Phillip L Campbell, Alisa E Koch

Published in: Arthritis Research & Therapy | Issue 2/2012

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Abstract

Introduction

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).

Conclusion

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.
Appendix
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Metadata
Title
Suppression of endothelial cell activity by inhibition of TNFα
Authors
Qiang Shu
Mohammad A Amin
Jeffrey H Ruth
Phillip L Campbell
Alisa E Koch
Publication date
01-04-2012
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 2/2012
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar3812

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