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Hemodynamic Regulation of Inflammation at the Endothelial–Neutrophil Interface

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Abstract

Arterial shear stress can regulate endothelial phenotype. The potential for anti-inflammatory effects of shear stress on TNFα-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/cm2 blocked by >80% the induction by 5 ng/mL TNFα of interleukin-8 (IL-8) and IL-6 secretion (50 and 90% reduction, respectively, in the presence of nitric oxide synthase antagonism with 200 μM nitro-l-arginine methylester, l-NAME). Exposure of TNFα-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/cm2. Also, neutrophil rolling lengths at 1 dyne/cm2 were longer when TNFα-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 NFκB, shear stress caused a marked 40-fold induction of luciferase in TNFα-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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Acknowledgments

This work was supported by National Institutes of Health Grant #HL64388 and #HL56621. J.Y.J. is a National Science Foundation Graduate Fellow and NIH Bioengineering Training Grant in Cardiovascular Physiology Recipient (5T32HL07954).

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Authors and Affiliations

  1. Department of Bioengineering, Institute for Medicine and Engineering, University of Pennsylvania, 1024 Vagelos Research Laboratory, 3340 Smith Walk, Philadelphia, PA, 19104, USA

    Julie Y. Ji & Scott L. Diamond

  2. Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, University of Pennsylvania, 1024 Vagelos Research Laboratory, 3340 Smith Walk, Philadelphia, PA, 19104, USA

    Huiyan Jing & Scott L. Diamond

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Correspondence to Scott L. Diamond.

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Ji, J.Y., Jing, H. & Diamond, S.L. Hemodynamic Regulation of Inflammation at the Endothelial–Neutrophil Interface. Ann Biomed Eng 36, 586–595 (2008). https://doi.org/10.1007/s10439-008-9465-4

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