Nicaraven inhibits TNFα-induced endothelial activation and inflammation through suppression of NF-κB signaling pathway

Inflammation-induced activation and dysfunction of endothelial cells play an important role in the pathology of multiple vascular diseases. Nicaraven, a potent hydroxyl radical scavenger, has recently been found to have anti-inflammatory roles; however, the mechanism of its action is not fully understood. Here we investigated the effects of Nicaraven on tumor necrosis factor alpha (TNF alpha) - induced inflammatory response in human umbilical vein endothelial cells and we explore the underlying mechanisms related to the nuclear factor-kappa B (NF-kappa B) signaling pathway. Our results showed that Nicaraven significantly reduced the reactive oxygen species production after TNF alpha stimulation. Nicaraven suppressed TNF alpha-induced mRNA expression of multiple adhesion molecules and pro-inflammatory cytokines, including vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E-selectin, MCP-1, TNF alpha, interleukin-1 beta (IL-1 beta), IL-6, and IL-8. In addition, Nicaraven inhibited monocyte adhesion and reduced the protein levels of VCAM-1 and ICAM-1. Mechanistically, Nicaraven prevented TNF alpha-induced activation of NF-kappa B signaling pathway by suppressing the phosphorylation of NF-kappa B p65, I kappa B alpha, and I kappa B kinase (IKK)alpha/beta, stabilizing I kappa B alpha, and inhibiting the translocation of p65 from cytosol to nucleus. Finally, we showed that Nicaraven improved the functions of endothelial cells, seen as the upregulation of endothelial nitric oxide synthase and increased nitric oxide levels. Our findings indicated that Nicaraven effectively inhibits TNF alpha-induced endothelial activation and inflammatory response at least partly through inhibiting NF-kappa B signaling pathway.

Automated summary

Nicaraven effectively inhibits TNF alpha-induced endothelial activation and inflammatory response by suppressing NF-kappa B signaling pathway, thereby improving endothelial cell functions.