alexa Apoptosis Resistance in Rheumatoid Arthritis Synovial T
ISSN: 2155-9899

Journal of Clinical & Cellular Immunology
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Review Article

Apoptosis Resistance in Rheumatoid Arthritis Synovial Tissue

Charles J. Malemud*
Department of Medicine, Division of Rheumatic Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
Corresponding Author : Charles J. Malemud
Professor of Medicine & Anatomy, Department of Medicine
Division of Rheumatic Diseases, University Hospitals Case Medical Center
Foley Medical Building, 2061 Cornell Road
Cleveland, Ohio 44106-5076, USA
Tel: (216) 844-7846
Fax: (216) 844-2288
E-mail: [email protected]
Received August 11, 2011; Accepted December 20, 2011; Published December 21, 2011
Citation: Malemud CJ (2011) Apoptosis Resistance in Rheumatoid Arthritis Synovial Tissue. J Clin Cell Immunol S3:006. doi:10.4172/2155-9899.S3-006
Copyright: © 2011 Malemud CJ. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Abstract

The pathogenesis of rheumatoid arthritis (RA) evolves from deregulated cellular and humoral immunity resulting in a chronic and systemic inflammatory response. Perpetuating the sustained inflammation in RA synovial joints requires the migration and retention of activated T-lymphocytes, B-lymphocytes, mast cells, neutrophils and antigen presenting cells. The synovial tissue becomes hyperplastic as a result of unrestrained synoviocyte proliferation and the resistance of synoviocytes, immune and inflammatory cells to apoptosis. Synoviocyte proliferation is mainly sustained by the elevated levels of pro-inflammatory cytokines in the RA synovial joint milieu. Thus, proinflammatory cytokines, including tumor necrosis factor-α, interleukin-(IL)-1β and IL-6, IL-17, interferon-γ, among others, predominantly activate the stress-activated protein kinase/mitogen-activated protein kinase (SAPK/MAPK) and the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathways which are known to cause the induction of apoptosis. However, activation of SAPK/MAPK and/or JAK/STAT pathways can also cause ‘cross-talk’ and activation of the phosphatidylinositol-3-kinase/Akt pathway which generally results in aberrant cell survival. The synovial tissue of RA synovial joints is also characterized by elevated levels of antiapoptosis proteins which suppress the apoptotic response. One of the main clinical responses of RA patients to therapy with methotrexate, sulfasalzine and leflunomide, or disease-modifying anti-rheumatic biological drugs, such as antagonists of tumor necrosis factor-α and the IL-6 receptor is actually to suppress the activation of signal transduction that inhibit apoptosis thereby reducing the survival of T- and B-cells, macrophages and inflammatory cells. In addition, several novel experimental strategies are also being considered with the view towards neutralizing those molecules held responsible for the resistance of synovial tissue to apoptosis. Thus, stimulating apoptosis may ameliorate arthritis. These targets include a group of tumor necrosis factor-related proteins, the BH3-only bcl-2 proteins, Fas ligand, cytokines such as IL-17 and IL-19, p53 up-regulated modulator of apoptosis and survivin.

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