oxidation in rheumatoid arthritis氧化在类风湿性关节炎.pdfVIP

Available online /content/6/6/265 Review Oxidation in rheumatoid arthritis Carol A Hitchon and Hani S El-Gabalawy Arthritis Centre and Rheumatic Diseases Research Laboratory University of Manitoba, Winnipeg, Manitoba, Canada Corresponding author: Hani El-Gabalawy, elgabal@cc.umanitoba.ca Published: 13 October 2004 Arthritis Res Ther 2004, 6:265-278 (DOI 10.1186/ar1447) © 2004 BioMed Central Ltd Abstract Oxygen metabolism has an important role in the pathogenesis of rheumatoid arthritis. Reactive oxygen species (ROS) produced in the course of cellular oxidative phosphorylation, and by activated phagocytic cells during oxidative bursts, exceed the physiological buffering capacity and result in oxidative stress. The excessive production of ROS can damage protein, lipids, nucleic acids, and matrix components. They also serve as important intracellular signaling molecules that amplify the synovial inflammatory–proliferative response. Repetitive cycles of hypoxia and reoxygenation associated with changes in synovial perfusion are postulated to activate hypoxia-inducible factor-1α and nuclear factor-κB, two key transcription factors that are regulated by changes in cellular oxygenation and cytokine stimulation, and that in turn orchestrate the expression of a spectrum of genes critical to the persistence of synovitis. An understanding of the complex interactions involved in these pathways might allow the development of novel therapeutic strategies for rheumatoid arthritis.