Abstract
Inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) have been known to be involved in various pathophysiological processes such as inflammation. This study was performed to determine the regulatory function of superoxide dismutase (SOD) on the LPS-induced expression of iNOS, and COX-2 in RAW 264.7 cells. When a cell-permeable SOD, Tat- SOD, was added to the culture medium of RAW 264.7 cells, it rapidly entered the cells in a dose-dependent manner. Treatment of RAW 264.7 cells with Tat-SOD led to decrease in LPS-induced ROS generation. Pretreatment with Tat-SOD significantly inhibited LPS-induced expression of iNOS and NO production but had no effect on the expression of COX-2 and PGE((2)) production in RAW 264.7 cells. Tat-SOD inhibited LPS-induced NF-kappaB DNA binding activity, IkappaBalpha degradation and activation of MAP kinases. These data suggest that SOD differentially regulate expression of iNOS and COX-2 in LPS-stimulated RAW 264.7 cells.
Highlights
Macrophages become activated by a variety of stimuli such as LPS and participate in the process of immune responses
We have demonstrated that the genetic in-frame Tat PTD-superoxide dismutase (Tat-SOD) was efficiently delivered in vitro and in vivo and exerted its biological effects (Eum et al, 2004; Song et al, 2008)
Since Reactive oxygen species (ROS) play a crucial role in the inflammation processes, in this study, we examined the potential regulatory effects of SOD on the redox-regulated NF-κB signaling pathway and the expression of proinflammatory genes such as Inducible nitric oxide synthase (iNOS) and COX-2 in the LPS-stimulated RAW 264.7 cells
Summary
Macrophages become activated by a variety of stimuli such as LPS and participate in the process of immune responses. Activated macrophages produce various inflammatory mediators such as cytokines/chemokines, nitric oxide (NO), and prostaglandin E2 (PGE2) (Reviewed in Guha and Mackman, 2001). Reactive oxygen species (ROS) is considered to be a causal factor in the inflammation responses induced by a variety of stimuli including LPS (Keller et al, 1999; Wang and Joseph, 1999). Cells maintain a balanced cellular redox state by using a complex ROS regulating network which is composed of antioxidant enzymes such as superoxide dismutase (SOD), catalase and glutathione peroxidase, and low molecular mass antioxidants such ascorbic acid, glutathione and tocopherols (Mates, 2000). SOD catalyzes the decomposition of superoxide to generate hydrogen peroxide that is subsequently converted to water and oxygen by glutathione peroxidase and catalase (Halliwell and Gutteridge, 1990)
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