Hemodynamic regulation of inflammation at the endothelial-neutrophil interface - PubMed (original) (raw)
Hemodynamic regulation of inflammation at the endothelial-neutrophil interface
Julie Y Ji et al. Ann Biomed Eng. 2008 Apr.
Free article
Abstract
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.
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