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The endothelium maintains normal barrier integrity and blood fluidity. The proinflammatory cytokines affect the endothelial function and endothelium-derived factors, leading to increased endothelial permeability, impaired nitric oxide (NO) production and altered adhesion molecule expressions. These are associated with the progression of several cardiovascular diseases such as atherosclerosis and hypertension. Interferon-gamma (IFN-γ) is a proinflammatory cytokine primarily released by T helper cells and cytotoxic T cells. This T-cell-derived cytokine has been shown to perpetuate the development of atherosclerosis and promote hypertension. However, the effect of IFN-γ on endothelial function remains to be investigated. The present study aimed to investigate the effect of IFN-γ on endothelial permeability, NO production and adhesion molecule expressions in human umbilical vein endothelial cells (HUVECs).HUVECs were challenged with 10 ng/ml of IFN-γ for 4–24 h and the permeability percentages, the NO levels and the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1) were determined using permeability assay kit, Griess assay and Western blot, respectively.Permeability assay showed that IFN-γ caused a biphasic increase in HUVECs permeability. The first phase of increased permeability occurred at 4–8 h and the second phase of increased permeability occurred at 16–24 h. The NO assay showed that IFN-γ significantly reduced both the basal NO levels and increased NO levels donated by sodium nitroprusside. Western blot analysis revealed that IFN-γ induced upregulation of ICAM-1 expression, which was started at 8 h, coinciding with downregulation of VCAM-1 expression. However, PECAM-1 expression remained unaltered.IFN-γ-induced endothelial dysfunction may be closely related to the impairment of barrier integrity, reduced NO bioavailability and altered cell phenotypes. These findings enrich the current knowledge on the mechanisms of IFN-γ in disrupting the endothelial function.