Endocrine Abstracts (2017) 50 P211 | DOI: 10.1530/endoabs.50.P211

Nuclear factor-kappa beta activation and monocyte-endothelial adhesion lead to chemerin induced endothelial cell inflammation

Georgios K Dimitriadis1,2, Jaspreet Kaur2, Maria Mytilinaiou1, Allan Davasgaium1, Diane Sambrook1, Claire Hewins1, Nilisha Nalawade1, Alexander D Miras3 & Harpal S Randeva1,2

1Department of Endocrinology Diabetes and Metabolism WISDEM Centre UHCW NHS Trust, Coventry, UK; 2Division of Translational and Experimental Medicine, Warwick Medical School, University of Warwick, Coventry, UK; 3Division of Endocrinology and Experimental Medicine, Imperial College London, Hammersmith Campus, London, UK.

Chemerin, a chemoattractant protein, acts via a G-protein coupled chemokine receptor, i.e. Chemokine like Receptor 1/ChemR23; levels of which are elevated in pro-inflammatory states such as obesity and type 2 diabetes mellitus (T2DM). Obesity and T2DM patients are at high risk of developing cardiovascular disorders such as atherosclerosis. We have reported that chemerin induces human endothelial cell angiogenesis and since dysregulated angiogenesis and endothelial dysfunction are hallmarks of vascular disease; we sought to determine the effects of chemerin on monocyte-endothelial adhesion, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a critical pro-inflammatory transcription factor. Human endothelial cells were transfected with pNF-kappaB-Luc plasmid. Chemerin induced NF-κB activation via the MAPK and PI3K/Akt pathways. Western blot analyses and monocyte-endothelial adhesion assay showed that chemerin increased endothelial cell adhesion molecule expression and secretion, namely E-selectin (Endothelial Selectin), VCAM-1 (Vascular Cell Adhesion Molecule-1) and ICAM-1 (Intracellular Adhesion Molecule-1), leading to enhancement of monocyte-endothelial adhesion. Additionally, we showed a synergistic response of the pro-inflammatory mediator, Interleukin-1β with chemerin induced effects. Chemerin plays an important role in endothelial inflammation, as it induces monocyte-endothelial adhesion, a critical step in the development of atherosclerosis.