Novel pathways that regulate tumor necrosis factor-alpha production in rheumatoid arthritis.
Clinical intervention studies have clearly shown the benefit in suppressing tumor necrosis factor-alpha (TNF-alpha) rheumatoid arthritis (RA). In consequence, considerable interest has arisen in those pathways that in turn regulate TNF-alpha production, because they may offer further possible therapeutic targets. Several candidate pathways are currently being investigated. They include T cell/macrophage interactions mediated primarily through cell-cell membrane contact; novel cytokine activities; microbial-derived products, in particular bacterial deoxyribonucleic acid sequences; autoreactive T cells, and immunoglobulins. At the subcellular level, there is further interest in targeting signaling and mRNA processing and cytokine cleavage pathways required for optimal TNF-alpha production. The key recent observations in these areas, particularly in the extracellular compartment, are reviewed.
Gracie
J Alastair
JA
Center for Rheumatic Diseases and Department of Immunology, University of Glasgow, Glasgow, UK.
Leung
Bernard P
BP
McInnes
Iain B
IB
D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000503:physiopathology; D018407:Bacterial Physiological Phenomena; D002450:Cell Communication / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D006801:Humans; D007425:Intracellular Membranes / Q000502:physiology; D008264:Macrophages / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000378:metabolism
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha