Gene interactions and pathways from curated databases and text-mining
Br J Pharmacol 2001, PMID: 11156586

N-acetylcysteine attenuates TNF-alpha-induced p38 MAP kinase activation and p38 MAP kinase-mediated IL-8 production by human pulmonary vascular endothelial cells.

Hashimoto, S; Gon, Y; Matsumoto, K; Takeshita, I; Horie, T

1. We have previously shown that tumour necrosis factor-alpha (TNF-alpha) activates p38 mitogen-activated protein (MAP) kinase to produce interleukin-8 (IL-8) by human pulmonary vascular endothelial cells. Reactive oxygen species (ROS) including H(2)O(2) generated by TNF-alpha can act as signalling intermediates for cytokine induction; therefore, scavenging ROS by anti-oxidants is important for the regulation of cytokine production. However, the effect of N-acetylcysteine (NAC), which acts as a precursor of glutathione (GSH) synthesis, on TNF-alpha-induced activation of p38 MAP kinase pathway and p38 MAP kinase-mediated IL-8 production by human pulmonary vascular endothelial cells has not been determined. To clarify these issues, we examined the effect of NAC on TNF-alpha-induced activation of p38 MAP kinase, MAP kinase kinase (MKK) 3 and MKK6 which are upstream regulators of p38 MAP kinase, and p38 MAP kinase-mediated IL-8 production. 2. Human pulmonary vascular endothelial cells that had been preincubated with NAC were stimulated with TNF-alpha and then the activation of p38 MAP kinase and MKK3/MKK6 in the cells and IL-8 concentrations in the culture supernatants were determined. 3. Intracellular GSH levels increased in NAC-treated cells. 4. NAC attenuated TNF-alpha-induced activation of p38 MAP kinase and MKK3/MKK6. 5. NAC attenuated p38 MAP kinase-mediated IL-8 production by TNF-alpha-stimulated cells. 6. These results indicate that the cellular reduction and oxidation (redox) regulated by intracellular GSH is critical for TNF-alpha-induced activation of p38 MAP kinase pathway and p38 MAP kinase-mediated IL-8 production by human pulmonary vascular endothelial cells, and we emphasize that anti-oxidant therapy is an important strategy for the treatment of acute lung injury.

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Text Mining Data

p38 → TNF-alpha: " N-acetylcysteine attenuates TNF-alpha induced p38 MAP kinase activation and p38 MAP kinase mediated IL-8 production by human pulmonary vascular endothelial cells "

mitogen activated protein ( MAP ) kinase → tumour necrosis factor-alpha (TNF-alpha): " 1. We have previously shown that tumour necrosis factor-alpha (TNF-alpha) activates p38 mitogen activated protein ( MAP ) kinase to produce interleukin-8 (IL-8) by human pulmonary vascular endothelial cells "

p38 → TNF-alpha: " However, the effect of N-acetylcysteine (NAC), which acts as a precursor of glutathione ( GSH ) synthesis, on TNF-alpha induced activation of p38 MAP kinase pathway and p38 MAP kinase mediated IL-8 production by human pulmonary vascular endothelial cells has not been determined "

IL-8 → TNF-alpha: " However, the effect of N-acetylcysteine (NAC), which acts as a precursor of glutathione ( GSH ) synthesis, on TNF-alpha induced activation of p38 MAP kinase pathway and p38 MAP kinase mediated IL-8 production by human pulmonary vascular endothelial cells has not been determined "

p38 — N-acetylcysteine (NAC): " However, the effect of N-acetylcysteine (NAC) , which acts as a precursor of glutathione ( GSH ) synthesis, on TNF-alpha induced activation of p38 MAP kinase pathway and p38 MAP kinase mediated IL-8 production by human pulmonary vascular endothelial cells has not been determined "

IL-8 — N-acetylcysteine (NAC): " However, the effect of N-acetylcysteine (NAC) , which acts as a precursor of glutathione ( GSH ) synthesis, on TNF-alpha induced activation of p38 MAP kinase pathway and p38 MAP kinase mediated IL-8 production by human pulmonary vascular endothelial cells has not been determined "

IL-8 → NAC: " To clarify these issues, we examined the effect of NAC on TNF-alpha induced activation of p38 MAP kinase, MAP kinase kinase (MKK) 3 and MKK6 which are upstream regulators of p38 MAP kinase, and p38 MAP kinase mediated IL-8 production "

MAP kinase kinase (MKK) 3 → TNF-alpha: " To clarify these issues, we examined the effect of NAC on TNF-alpha induced activation of p38 MAP kinase, MAP kinase kinase (MKK) 3 and MKK6 which are upstream regulators of p38 MAP kinase, and p38 MAP kinase mediated IL-8 production "

MAP kinase kinase (MKK) 3 — NAC: " To clarify these issues, we examined the effect of NAC on TNF-alpha induced activation of p38 MAP kinase, MAP kinase kinase (MKK) 3 and MKK6 which are upstream regulators of p38 MAP kinase, and p38 MAP kinase mediated IL-8 production "

p38 → TNF-alpha: " 6. These results indicate that the cellular reduction and oxidation ( redox ) regulated by intracellular GSH is critical for TNF-alpha induced activation of p38 MAP kinase pathway and p38 MAP kinase mediated IL-8 production by human pulmonary vascular endothelial cells, and we emphasize that anti-oxidant therapy is an important strategy for the treatment of acute lung injury "

IL-8 → TNF-alpha: " 6. These results indicate that the cellular reduction and oxidation ( redox ) regulated by intracellular GSH is critical for TNF-alpha induced activation of p38 MAP kinase pathway and p38 MAP kinase mediated IL-8 production by human pulmonary vascular endothelial cells, and we emphasize that anti-oxidant therapy is an important strategy for the treatment of acute lung injury "

Manually curated Databases

No curated data.