Differential regulation of inducible nitric oxide synthase and cyclooxygenase-2 expression by superoxide dismutase in lipopolysaccharide stimulated RAW 264.7 cells

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 PGE2 production in RAW 264.7 cells. Tat-SOD inhibited LPS-induced NF-κB DNA binding activity, IκBα 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.

Suppression of TNF-alpha-induced MMP-9 expression by a cell-permeable superoxide dismutase in keratinocytes

“…Consistent with our results, a cell-permeable catalase with nine arginine residues was previously shown to suppress TNF-α-induced production of cytokines, such as IL-8 and IL-6, in primary human keratinocytes (11). We previously reported that Tat-SOD exerts anti-inflammatory responses by inhibiting expression of pro-inflammatory mediators such as iNOS and COX-2 in LPS-stimulated macrophages (16,17). Taken together, these studies demonstrated that availability of cell-permeable antioxidant enzymes, such as SOD and catalase, sig-http://bmbreports.org BMB reports nificantly contribute to the development of therapeutic tools for controlling ROS-mediated inflammation.…”

“…A cell-permeable Tat-SOD was previously shown to efficiently enter cells and tissues, exerting its protective effect against oxidative stress (16)(17)(18). To assess the amount of SOD fusion proteins taken up into the cells, SOD fusion proteins at concentrations ranging from 0.25 to 2 μM were added to the culture medium of HaCaT cells for 1 h, after which cell lysates were prepared and analyzed by Western blotting.…”

“…14,15). Previous studies demonstrated that Tat-SOD is capable of inhibiting ROS generation in various types of cells under oxidative stress (16)(17)(18). Recently, it was demonstrated that a cell-permeable catalase attenuates TNF-α-induced production of cytokines such as IL-8, IL-6, and TNF-α itself in primary human keratinocytes (11).…”

The Effect of Docosahexaenoic Acid on Visual Evoked Potentials in a Mouse Model of Parkinson’s Disease: The Role of Cyclooxygenase-2 and Nuclear Factor Kappa-B

“…However, a large amount of evidence suggested an important role for oxygen free radical and oxidative stress in the pathogenesis of PD (Schapira et al 1990). Increased levels of reactive oxygen species (ROS) which in turn activates redox-sensitive transcriptional factors such as nuclear factor kappa-B (NF-jB) (Lee et al 2009a) leads to expression of many pro-inflammatory genes including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Increased nuclear translocation of NF-jBp65 has previously been demonstrated in dopaminergic neurons of PD mice (Hunot et al 2004;Ghosh et al 2007).…”

Phenotypic Modulation of Mesenteric Vascular Smooth Muscle Cells from Type 2 Diabetic Rats is Associated with Decreased Caveolin-1 Expression

“…To investigate the effect of HG on ROS generation, quiescent mesenteric VSMCs were treated with HG or NG for 12 hours. In another set of experiments, to measure ROS generation and ERK1/2 activation, quiescent cells were stimulated with LPS (100 ng/mL) for 15 minutes [25,26]. …”