| Autor: |
Cuzzocrea, Salvatore, Pisano, Barbara, Dugo, Laura, Ianaro, Angela, Ndengele, Michael, Salvemini, Daniela |
| Zdroj: |
Antioxidants and Redox Signaling; August 01, 2004, Vol. 6 Issue: 4 p699-704, 6p |
| Abstrakt: |
The nuclear factor-κB (NF-κB) is a transcription factor that plays a pivotal role in the induction of genes involved in physiological processes, as well as in the response to inflammation. In this study, we used a selective nonpeptidyl superoxide dismutase mimetic, M40403, to investigate the role of superoxide anion in NF-κB activation during acute inflammation in mice. Injection of carrageenan into the pleural cavity of mice induced an acute inflammatory response characterized by fluid accumulation in the pleural cavity that contained a large number of neutrophils, as well as an increased production of tumor necrosis factor-α and interleukin-1β. All parameters of inflammation were attenuated by M40403 (10 mg/kg i. p., 30 min prior to carrageenan administration). These inflammatory events were associated with the activation of NF-κB in the lung. In particular, the appearance of inhibitory protein κB-α (IκB-α) in homogenates of lung tissues was investigated by immunoblot analysis at 4 h after carrageenan administration. IκB-α levels were substantially reduced in the lung tissue from carrageenan-treated mice in comparison with sham-treated mice. Furthermore, to detect NF-κB/DNA binding activity, whole extracts from lung tissue of each mouse were analyzed by electrophoretic mobility-shift assay. The DNA binding activity significantly increased in whole extracts obtained from lung tissues of vehicle-treated mice 4 h after carrageenan administration. Treatment of mice with M40403 caused a significant inhibition of carrageenan-induced IκB-α degradation and NF-κB/DNA binding activity. These data confirm that M40403 exerts a potent antiinflammatory activity and clearly demonstrate that the reduction of the inflammatory process is associated with modification of the activation of signal transduction pathways. |
| Databáze: |
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