Tocilizumab,a Humanized Monoclonal Antibody Against the Interleukin-6 Receptor,Inhibits High Glucose-Induced Vascular Smooth Muscle Cell Migration Through Mitogen-Activated Protein Kinase Signaling Pathways
Restricted accessResearch articleFirst published online November, 2018
Tocilizumab,a Humanized Monoclonal Antibody Against the Interleukin-6 Receptor,Inhibits High Glucose-Induced Vascular Smooth Muscle Cell Migration Through Mitogen-Activated Protein Kinase Signaling Pathways
Rheumatoid arthritis (RA) with diabetes increases the risk of cardiovascular diseases. Interleukin-6 (IL-6) promotes the disease activity of RA and insulin resistance. This study aimed to evaluate the potential effects and molecular mechanisms of IL-6 blocker, tocilizumab, in atherosclerosis with diabetes. Human aortic smooth muscle cells (HASMCs) cultured under hyperglycemic conditions were evaluated for migration, expression of adhesion molecules, and matrix metalloproteinases before and after treatment with tocilizumab. High glucose (HG) significantly increased expression of IL-6, intercellular adhesion molecule (ICAM-1), matrix metalloproteinase-2 & 9, and migration of vascular smooth muscle cells. Tocilizumab suppressed HG-induced expression of ICAM-1, MMP-2, and MMP-9. Pretreatment with tocilizumab also inhibited migration, MAPK signaling, and nuclear translocation of p65-NF-κB in HG-stimulated HASMCs. Our data suggested that tocilizumab may exert an antiatherosclerotic activity in diabetes.
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