Aberrant Reactive Oxygen and Nitrogen Species Generation in Rheumatoid Arthritis (RA): Causes and Consequences for Immune Function, Cell Survival, and Therapeutic Intervention
- 15 March 2010
- journal article
- review article
- Published by Mary Ann Liebert Inc in Antioxidants and Redox Signaling
- Vol. 12 (6), 743-785
- https://doi.org/10.1089/ars.2009.2607
Abstract
The infiltration and persistence of hematopoietic immune cells within the rheumatoid arthritis (RA) joint results in elevated levels of pro-inflammatory cytokines, increased reactive oxygen (ROS) and -nitrogen (RNS) species generation, that feeds a continuous self-perpetuating cycle of inflammation and destruction. Meanwhile, the controlled production of ROS is required for signaling within the normal physiological reaction to perceived “foreign matter” and for effective apoptosis. This review focuses on the signaling pathways responsible for the induction of the normal immune response and the contribution of ROS to this process. Evidence for defects in the ability of immune cells in RA to regulate the generation of ROS and the consequence for their immune function and for RA progression is considered. As the hypercellularity of the rheumatoid joint and the associated persistence of hematopoietic cells within the rheumatoid joint are symptomatic of unresponsiveness to apoptotic stimuli, the role of apoptotic signaling proteins (specifically Bcl-2 family members and the tumor suppressor p53) as regulators of ROS generation and apoptosis are considered, evaluating evidence for their aberrant expression and function in RA. We postulate that ROS generation is required for effective therapeutic intervention. Antioxid. Redox Signal. 12, 743–785.Keywords
This publication has 303 references indexed in Scilit:
- Bz-423 superoxide signals apoptosis via selective activation of JNK, Bak, and BaxFree Radical Biology & Medicine, 2008
- Antioxidant intervention in rheumatoid arthritis: results of an open pilot studyClinical Rheumatology, 2008
- The BCL-2 protein family: opposing activities that mediate cell deathNature Reviews Molecular Cell Biology, 2008
- Rab27a regulates phagosomal pH and NADPH oxidase recruitment to dendritic cell phagosomesNature, 2007
- ATP Activates a Reactive Oxygen Species-dependent Oxidative Stress Response and Secretion of Proinflammatory Cytokines in MacrophagesPublished by Elsevier BV ,2007
- T cell surface redox levels determine T cell reactivity and arthritis susceptibilityProceedings of the National Academy of Sciences of the United States of America, 2006
- Differential survival of leukocyte subsets mediated by synovial, bone marrow, and skin fibroblasts: Site‐specific versus activation‐dependent survival of T cells and neutrophilsArthritis & Rheumatism, 2006
- Reactive oxygen species mediate crosstalk between NF-κB and JNKCell Death & Differentiation, 2005
- Essential role of BAX,BAK in B cell homeostasis and prevention of autoimmune diseaseProceedings of the National Academy of Sciences of the United States of America, 2005
- Evolving concepts of rheumatoid arthritisNature, 2003