Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Toll-Like Receptor 2 Activation Induces Angiogenesis, ICAM-1 Expression and EC Invasion in Rheumatoid Arthritis.
Saber2, Tajvur P., NicUltaigh3, Sinead, McCormick2, Jennifer, Veale4, Douglas J., Connolly2, Mary, Fearon1, Ursula
Angiogenesis is a critical early event in inflammatory arthritis, facilitating leukocyte migration into the synovium resulting in invasion and destruction of articular cartilage and bone. This study investigates the effect of TLR2 on angiogenesis, EC adhesion and invasion using microvascular endothelial cells and RA whole tissue synovial explants ex-vivo.
Microvascular endothelial cells (HDEC) and RA synovial explants ex vivo were cultured with the TLR2 ligand, Pam3CSK4 (1mg/ml). HDEC tube formation was assessed using Matrigel matrix assays. Angiopoietin 2 (Ang2) was measured by ELISA. ICAM-1 cell surface expression was assessed by flow cytometry. Cell migration was assessed by wound repair scratch assays. ECM invasion, MMP-2 and 9 expression were assessed using transwell invasion chambers and zymography.
Pam3CSK4 significantly increased angiogenenic tube formation (p<0.05). Pam3CSK4 significantly upregulated Ang2 production in HDEC (p<0.05) and RA synovial explants (p<0.05). Pam3CSK4 induced cell surface expression of ICAM-1, from basal level of 149 ± 54 (MFI) to 617±103 (p<0.01). TLR-2 activation induced an 8.8 ± 2.8 fold increase in cell invasion compared to control (p<0.05). Pam3CSK also induced cell migration and induced MMP-2 and -9 from RA synovial explants. Neutralisation of TLR2 with a blocking monoclonal antibody (OPN 301, 1mg/ml) inhibited Pam3CSK4-induced wound repair and EC tube formation.
Pam3CSK4 activation of TLR2 promotes angiogenesis, cell adhesion and invasion, key mechanisms involved in the pathogenesis of RA.
To cite this abstract, please use the following information:
Saber, Tajvur P., NicUltaigh, Sinead, McCormick, Jennifer, Veale, Douglas J., Connolly, Mary, Fearon, Ursula; Toll-Like Receptor 2 Activation Induces Angiogenesis, ICAM-1 Expression and EC Invasion in Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1391