Superoxide-related signaling cascade mediates nuclear factor-kappaB activation in acute inflammation

Antioxidants & Redox Signaling
Salvatore CuzzocreaD Salvemini

Abstract

The nuclear factor-kappaB (NF-kappaB) 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-kappaB 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-alpha and interleukin-1beta. 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-kappaB in the lung. In particular, the appearance of inhibitory protein kappaB-alpha (IkappaB-alpha) in homogenates of lung tissues was investigated by immunoblot analysis at 4 h after carrageenan administration. IkappaB-alpha levels were substantially reduced in the lung tissue from carrageenan-treated mice in comparison with sham-treated mice. Furthermore, to detect NF-kappaB/DNA b...Continue Reading

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Citations

Jul 10, 2004·Antioxidants & Redox Signaling·Agnes Görlach
Aug 24, 2005·Antioxidants & Redox Signaling·Agnes Görlach
Jan 26, 2010·Antioxidants & Redox Signaling·Ines Batinić-HaberleIvan Spasojević
Jul 2, 2010·Mediators of Inflammation·Masahiro IwataKenji Takagi
Feb 27, 2009·Naunyn-Schmiedeberg's Archives of Pharmacology·Emanuela MazzonSalvatore Cuzzocrea
Feb 26, 2016·Neuropharmacology·Felipe A Pinho-RibeiroWaldiceu A Verri
Nov 20, 2008·Archives of Biochemistry and Biophysics·Daniela Salvemini
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Jan 13, 2005·The Journal of Pharmacology and Experimental Therapeutics·Tiziana GenoveseSalvatore Cuzzocrea

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