title: The effect of interferon γ on endothelial cell nitric oxide production and apoptosis.
abstract: BACKGROUND
  Nitric oxide (NO) is an important molecule in maintaining endothelial survival and normal function. It is a unique mediator, which may promote or suppress both inflammation and apoptosis. Endothelial cell (EC) injury, dysfunction, and death in response to cytokines, especially interferon gamma (IFN-γ), represent the critical event for the initiation of several inflammatory diseases.
  
  
  OBJECTIVE
  EC injury or death result in endothelial dysfunction that precedes the development of atherosclerosis and its subsequent vascular events. We examine the effect of different concentrations of IFN-γ on human umbilical vein ECs (HUVECs) NO production and apoptosis.
  
  
  METHODS
  HUVECs were cultured at 37°C for 24 h in the absence (control) or presence of 10, 100, and 1000 μg IFN-γ, respectively. The apoptotic cells were determined as annexin V-positive propidium iodide (PI)-negative cells by flow cytometry. Total nitrite concentration was measured in cell cultures supernatant by Griess method.
  
  
  RESULTS
  A comparison of the effect of IFN-γ on EC NO production with untreated cells showed that pretreatment of HUVEC with IFN-γ failed to have a significant effect on NO production by these cells at 10 and 100 U/mL, whereas it led to a significant decreased NO production at 1000 U/mL (P < 0.05). The cells stimulated with IFN-γ showed significantly higher apoptotic cells (PI negative and annexin V-positive cells) after 24 h, compared with cells with no stimulations (P < 0.05).
  
  
  CONCLUSIONS
  IFN-γ has detrimental effects on ECs in high doses. This might be due to inducible NO synthase activation.
authors: Department of physiology, Isfahan university of medical sciences, Isfahan, Iran.
authors: Shaghayegh Haghjooy
authors: SH
authors: Javanmard
authors: Nasim
authors: N
authors: Dana
keywords: Apoptosis; IFN-γ; endothelial cells; nitric oxide