Nordihydroguaiaretic acid attenuates TNFα-dependent intercellular adhesion molecule-۱ expression in cultured human umbilical vein endothelial cells via targeting TNFα-PI۳K-NF-κB-ICAM۱ pathway

Objective: During inflammation and oxidative stress, vascular endothelial cell surfaces express high levels of adhesion molecules such as intercellular adhesion molecule ۱ (ICAM۱) which bind the circulatory leukocytes (e.g. macrophages), through counter receptors LFA/Mac۱. The bound leukocytes on sub-endothelial translocation accumulate oxidized lipids and proteins, developing atherosclerotic plaques by foam cell and fatty streak formations. Herewith, nordihydroguaiaretic acid (NDGA) prevails as a polyphenol in the Larrea tridentata plant, with potent antioxidant and anti-inflammatory traits. This study for the first time elucidates that NDGA attenuates TNFα-dependent ICAM۱ expression in the cultured human umbilical vein endothelial cells (HUVECs), by targeting the TNFα-PI۳K-NF-κB-ICAM۱ pathway.Materials and Methods: Cultured HUVECs were treated with pro-inflammatory and pro-oxidative cytokine TNFα, to induce ICAM۱ mRNA level and protein expression on HUVECs cell surface as documented by northern and western blot, respectively. The effect of varying NDGA concentrations was examined on TNFα-stimulated ICAM۱ expression and monocyte attachment assay.Results: Pre-TNFα-NDGA treatment of HUVECs moderated TNFα-dependent ICAM۱ expression and monocyte attachment on vascular endothelium by inhibiting the PI۳K-NF-κB-ICAM۱ signaling pathway.Conclusion: In this study, the NDGA anti-inflammatory and anti-adhesion essence is elucidated via impaired cytoplasm to nucleus  translocation of pro-oxidative and pro-inflammatory transcription factor NF-κB, moderating the ICAM۱ expression and monocyte attachment.

کلیدواژه ها:

Human umbilical vein endothelial cells (HUVECs) TNFα Intercellular adhesion molecule ، ۱ (ICAM۱) NDGA PI۳K NF ، κB