Interleukin-10-mediated inhibition of free radical generation in macrophages

Sujatha Dokka, Xianglin Shi, Stephen Leonard, Liying Wang, Vincent Castranova, Yon Rojanasakul

Research output: Contribution to journalArticlepeer-review

100 Scopus citations


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-κB (NF-κB). Although still controversial, IL-10 has been shown to inhibit NF-κB activation through a process that involves proteolytic degradation of inhibitory subunit IκB-α. What is not known, however, is the mechanism by which IL-10 exerts its effect on IκB-α degradation. The present study investigates the possible role of reactive oxygen species (ROS) and their inhibition by IL-10 in NF-κB activation and IκB-α degradation in macrophages. Treatment of the cells with lipopolysaccharide (LPS) caused activation of NF-κB and rapid proteolysis of IκB-α as determined by the electrophoretic mobility shift assay, gene transfection, and Western blot. IL-10 pretreatment inhibited both NF-κB activation and IκB-α 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-2 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 IκB-α 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-κB activation.

Original languageEnglish
Pages (from-to)L1196-L1202
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number6 24-6
StatePublished - 2001


  • Nuclear factor-κB
  • Oxygen free radicals
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


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