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Interleukin-10-mediated Inhibition of free radical generation in macrophages.
Dokka S; Shi X; Leonard S; Wang L; Castranova V; Rojanasakul Y
Am J Physiol, Lung Cell Mol Physiol 2001 Jun; 280(6):L1196-L1202
Interleukin-10 (IL-10) is a pleiotropic cytokine that controls inflammatory processes by suppressing the production of proinflammatory cytokines that are known to be transcriptionally regulated by nuclear factor-B (NF-B). Although still controversial, IL-10 has been shown to inhibit NF-B activation through a process that involves proteolytic degradation of inhibitory subunit IB-. What is not known, however, is the mechanism by which IL-10 exerts its effect on IB- degradation. The present study investigates the possible role of reactive oxygen species (ROS) and their inhibition by IL-10 in NF-B activation and IB- degradation in macrophages. Treatment of the cells with lipopolysaccharide (LPS) caused activation of NF-B and rapid proteolysis of IB- as determined by the electrophoretic mobility shift assay, gene transfection, and Western blot. IL-10 pretreatment inhibited both NF-B activation and IB- degradation. Both of these processes were also inhibited by ROS scavengers, catalase (H2O2 scavenger), and sodium formate (·OH scavenger) but were minimally affected by superoxide dismutase (O scavenger). These results suggests that ·OH radicals, formed by an H2O2-dependent, metal-catalyzed Fenton reaction, play a major role in this process. Electron spin resonance studies confirmed the formation of ·OH radicals in LPS-treated cells. Addition of IL-10 inhibited both IB- degradation and generation of ·OH radicals in response to LPS stimulation. These results demonstrate, for the first time, direct evidence for the role of IL-10 in ROS-dependent NF-B activation.
Molecular-biology; Regulations; Diseases; Animal-studies; Immune-system; Free-radicals; Free-radical-generation; Animals; Author Keywords: nuclear factor-kB; tumor necrosis factor-a; oxygen free radicals
Y. Rojanasakul, West Virginia University School of Pharmacy, Department of Basic Pharmaceutical Sciences, P.O. Box 9530, Morgantown, WV 26506
Issue of Publication
American Journal of Physiology: Lung Cellular and Molecular Physiology
Page last reviewed: September 2, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division