J Korean Med Sci.  1999 Jun;14(3):231-238. 10.3346/jkms.1999.14.3.231.

Nuclear factor kappaB (NF-kappaB) pathway as a therapeutic target in rheumatoid arthritis

• Jue DM
• Jeon KI
• Jeong JY

• KMID: 646299
• DOI: http://doi.org/10.3346/jkms.1999.14.3.231

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint swelling and progressive destruction of cartilage and bone. Current RA treatments are largely empirical in origin and their precise mechanism of action is uncertain. Increasing evidence shows that chronic inflammatory diseases such as RA are caused by prolonged production of proinflammatory cytokines including tumor necrosis factor (TNF) and interleukin 1 (IL-1). The nuclear factor kappaB (NF-kappaB) plays an essential role in transcriptional activation of TNF and IL-1. NF-kappaB is induced by many stimuli including TNF and IL-1, forming a positive regulatory cycle that may amplify and maintain RA disease process. NF-kappaB and enzymes involved in its activation can be a target for anti-inflammatory treatment. Aspirin and sodium salicylate inhibit activation of NF-KB by blocking IkappaB kinase, a key enzyme in NF-kappaB activation. Glucocorticoids suppress expression of inflammatory genes by binding glucocorticoid receptor with NF-kappaB, and increasing expression of inhibitory protein of NF-kappaB, IkappaBalpha. Sulfasalazine and gold compounds also inhibit NF-kappaB activation. Continuing advances in our understanding of action mechanism of antirheumatic agents will benefit the future development of RA regimens with greater efficacy and less toxicity.

Keyword

Tumor necrosis factor; NF-kappa B; Arthritis, rheumatoid; Interleukin 1; Monokines; Anti-inflammatory agents; Antirheumatic agents

MeSH Terms

Animal
Antirheumatic Agents/therapeutic use*
Arthritis, Rheumatoid/therapy*
Arthritis, Rheumatoid/metabolism
Arthritis, Rheumatoid/immunology
Cytokines/immunology
Cytokines/genetics
Gene Expression Regulation
Human
Macrophages/immunology
NF-kappa B/metabolism*
NF-kappa B/immunology
NF-kappa B/biosynthesis
Tumor Necrosis Factor/genetics