Redox-sensitive transcription factors play a significant role in the development of rheumatoid arthritis

Le Rossignol, Scott, Ketheesan, Natkunam, and Nagaraja, Haleagrahara (2018) Redox-sensitive transcription factors play a significant role in the development of rheumatoid arthritis. International Reviews of Immunology, 37 (3). pp. 129-143.

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Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease which is associated with significant morbidity. Redox sensitive transcription factors including NF-κB, HIF, AP-1, and Nrf2 are intimately involved in the pathogenesis of RA. The treatment of this disease is limited by the elusive nature of the pathogenesis of RA. NF-κB is crucial for the maturation of immune cells as well as production of TNFα and MMPs, which escalate RA. HIF is essential for activation of inflammatory cells, angiogenesis and pannus formation in RA. AP-1 regulates cytokine and MMP production as well as synovial hyperplasia which are key processes in RA. Nrf2 is involved with chondrogenesis, osteoblastogenesis, prostaglandin secretion and ROS production in RA. Targeting two or more of these transcription factors may result in increased efficacy than either therapy in isolation. This review will highlight the control specific mediators on these transcription factors, the subsequent effect of these transcription factors once activated, and then mesh this with the pathogenesis of RA. The elucidation of key transcription factor regulation in the pathogenesis of RA may highlight the novel therapy interventions which may prove to have a greater efficacy than those therapies currently available.

Item ID: 50548
Item Type: Article (Research - C1)
ISSN: 1563-5244
Keywords: rheumatoid arthritis; inflammatin; transcription factors; oxidative stress; cytokines
Funders: Arthritis Australia (AA), Australian Institute of Tropical Health and Medicine (AITHM)
Projects and Grants: AA HJ and GJ McKenzie Grant 2013
Date Deposited: 22 Sep 2017 05:11
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320403 Autoimmunity @ 25%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320223 Rheumatology and arthritis @ 75%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 25%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920116 Skeletal System and Disorders (incl. Arthritis) @ 75%
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