Suppression of endothelial cell activity by inhibition of TNFα

IntroductionTNFα 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.MethodsHuman 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.ResultsCertolizumab 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).ConclusionOur 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.

• Publication year

  2012

• Venue

  Arthritis Research & Therapy

• Publication date

  2012-04-25

• Fields of study

  Medicine

• Identifiers
  DOI 10.1186/ar3812PMID 22534470PMCID 3446462
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2008influential reference
• Certolizumab pegol plus methotrexate is significantly more effective than placebo plus methotrexate in active rheumatoid arthritis: findings of a fifty-two-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study.

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  2007influential reference
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  2005influential reference
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  2000cited by this paper
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  1999cited by this paper
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  1999cited by this paper
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  1999cited by this paper
• Expression of endothelial cell IgG Fc receptors and markers on various cultures.

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  1999cited by this paper
• Constitutive expression of E- and P-selectin cognate ligands in human endothelial cells.

  1998cited by this paper
• Angiogenesis in Rheumatoid Arthritis: Pathogenic and Clinical Significance

  1998cited by this paper
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  1996cited by this paper
• Cooperative effect of TNFalpha, bFGF, and VEGF on the formation of tubular structures of human microvascular endothelial cells in a fibrin matrix. Role of urokinase activity

  1996cited by this paper
• Decrease in cellularity and expression of adhesion molecules by anti-tumor necrosis factor alpha monoclonal antibody treatment in patients with rheumatoid arthritis.

  1996cited by this paper
• Deactivation of vascular endothelium by monoclonal anti-tumor necrosis factor alpha antibody in rheumatoid arthritis.

  1996cited by this paper
• Growth-related gene product alpha. A chemotactic cytokine for neutrophils in rheumatoid arthritis.

  1995cited by this paper
• Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1

  1995cited by this paper
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  1995cited by this paper
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• Intercellular adhesion molecule‐1 (ICAM‐1) expression and soluble ICAM‐1 (sICAM‐1) production by cytokine‐activated human aortic endothelial cells: a possible role for ICAM‐1 and sICAM‐1 in atherosclerotic aortic aneurysms

  1994cited by this paper
• Epithelial neutrophil activating peptide-78: a novel chemotactic cytokine for neutrophils in arthritis.

  1994cited by this paper
• Monocyte-endothelial adhesion in chronic rheumatoid arthritis. In situ detection of selectin and integrin-dependent interactions.

  1993cited by this paper
• Localization of tumor necrosis factor receptors in the synovial tissue and cartilage-pannus junction in patients with rheumatoid arthritis. Implications for local actions of tumor necrosis factor alpha.

  1992cited by this paper
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  1992cited by this paper
• Regulation of vascular cell adhesion molecule 1 on human dermal microvascular endothelial cells.

  1992cited by this paper
• Localization of tumor necrosis factor alpha in synovial tissues and at the cartilage-pannus junction in patients with rheumatoid arthritis.

  1991cited by this paper
• Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis.

  1991cited by this paper
• Immunolocalization of endothelial and leukocyte adhesion molecules in human rheumatoid and osteoarthritic synovial tissues.

  1991cited by this paper
• Inhibitory effect of TNF alpha antibodies on synovial cell interleukin-1 production in rheumatoid arthritis.

  1989cited by this paper
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  1989cited by this paper
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  1988cited by this paper
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  1987cited by this paper
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  1986cited by this paper
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