Affiliation:
1. Department of Biomedical Science, Faculty of Medicine and Health Sciences, Serdang, Selangor, Malaysia
Abstract
The endothelial barrier function is tightly controlled by a broad range of signaling cascades including nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway. It has been proposed that disturbances in NO and cGMP production could interfere with proper endothelial barrier function. In this study, we assessed the effect of interferon-gamma (IFN-γ), a pro-inflammatory cytokine, on NO and cGMP levels and examined the mechanisms by which NO and cGMP regulate the IFN-γ-mediated HUVECs hyperpermeability. The flux of fluorescein isothiocyanate-labeled dextran across cell monolayers was used to study the permeability of endothelial cells. Here, we found that IFN-γ significantly attenuated basal NO concentration and the increased NO levels supplied by a NO donor, sodium nitroprusside (SNP). Besides, application of IFN-γ also significantly attenuated both the basal cGMP concentration and the increased cGMP production donated by a cell permeable cGMP analogue, 8-bromo-cyclic GMP (8-Br-cGMP). In addition, exposure of the cell monolayer to IFN-γ significantly increased HUVECs basal permeability. However, L-NAME pretreatment did not suppress IFN-γ-induced HUVECs hyperpermeability. L-NAME pretreatment followed by SNP or SNP pretreatment partially reduced IFN-γ-induced HUVECs hyperpermeability. Pretreatment with a guanylate cyclase inhibitor, 6-anilino-5,8-quinolinedione (LY83583), led to a further increase in IFN-γ-induced HUVECs hyperpermeability. The findings suggest that the mechanism underlying IFN-γ-induced increased HUVECs permeability is partly related to the inhibition of NO production.
Publisher
Institute of Physiology of the Czech Academy of Sciences
Subject
General Medicine,Physiology
Reference24 articles.
1. ABE Y, SEKIYA S, YAMASITA T, SENDO F: Vascular hyperpermeability induced by tumor necrosis factor and its augmentation by IL-1 and IFN-gamma is inhibited by selective depletion of neutrophils with a monoclonal antibody. J Immunol 145: 2902-2907, 1990.
2. BOIVIN MA, ROY PK, BRADLEY A, KENNEDY JC, RIHANI T, MA TY: Mechanism of interferon-gamma-induced increase in T84 intestinal epithelial tight junction. J Interferon Cytokine Res 29: 45-54, 2009.
3. CHAVEZ AM, MENCONI MJ, HODIN RA, FINK MP: Cytokine-induced intestinal epithelial hyperpermeability: role of nitric oxide. Crit Care Med 27: 2246-2251, 1999.
4. CORREA CR, DIAS-MELICIO LA, CALVI SA, LASTORIA S, SOARES AM: Activation of monocytes and cytokine production in patients with peripheral atherosclerosis obliterans. J Inflamm (Lond) 8: 23, 2011.
5. DRAIJER R, ATSMA DE, VAN DER LAARSE A, VAN HINSBERGH VW: cGMP and nitric oxide modulate thrombin-induced endothelial permeability. Regulation via different pathways in human aortic and umbilical vein endothelial cells. Circ Res 76: 199-208, 1995.
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