Hemodynamic regulation of inflammation at the endothelial-neutrophil interface.
Arterial shear stress can regulate endothelial phenotype. The potential for anti-inflammatory effects of shear stress on TNFalpha-activated endothelium was tested in assays of cytokine expression and neutrophil adhesion. In cultured human aortic endothelial cells (HAEC), arterial shear stress of 10 dyne/cm(2) blocked by >80% the induction by 5 ng/mL TNFalpha of interleukin-8 (IL-8) and IL-6 secretion (50 and 90% reduction, respectively, in the presence of nitric oxide synthase antagonism with 200 microM nitro-L-arginine methylester, L-NAME). Exposure of TNFalpha-stimulated HAEC to arterial shear stress for 5 h also reduced by 60% (p < 0.001) the conversion of neutrophil rolling to firm arrest in a venous flow assay conducted at 1 dyne/cm(2). Also, neutrophil rolling lengths at 1 dyne/cm(2) were longer when TNFalpha-stimulated HAEC were presheared for 5 h at arterial stresses. In experiments with a synthetic promoter that provides luciferase induction to detect cis interactions of glucocorticoid receptor (GR) and NFkappaB, shear stress caused a marked 40-fold induction of luciferase in TNFalpha-treated cells, suggesting a role for GR pathways in the anti-inflammatory actions of fluid shear stress. Hemodynamic force exerts anti-inflammatory effects on cytokine-activated endothelium by attenuation of cytokine expression and neutrophil firm arrest.
Ji
Julie Y
JY
Department of Bioengineering, Institute for Medicine and Engineering, University of Pennsylvania, 1024 Vagelos Research Laboratory, 3340 Smith Walk, Philadelphia, PA 19104, USA.
Jing
Huiyan
H
Diamond
Scott L
SL
D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology*; D005246:Feedback; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000276:immunology*; D018375:Neutrophil Activation / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D033081:Shear Strength; D013314:Stress, Mechanical; D014657:Vasculitis / Q000276:immunology*
D016207:Cytokines