Signal transduction in rheumatoid arthritis.
Extracellular signals are transduced intracellularly by multiple pathways, resulting in alterations in the transcription and translation of specific proteins. The end result of some of these signalling pathways is the production of proteins, including cytokines and matrix metalloproteinases, that are implicated in the pathogenesis of rheumatoid arthritis. This chapter includes a discussion of these signal transduction pathways, including tumour necrosis factor receptor signalling, interleukin-1, -4, and -6 receptor signalling, stress- and mitogen-activated protein kinase pathways, CD14 and Toll-like receptor signalling, and T cell signal transduction. The known effects of currently available rheumatoid arthritis (RA) therapeutics on these signalling pathways are also reviewed. In addition, potential future targets for therapeutic intervention in RA are discussed.
Piecyk
M
M
Division of Rheumatology and Immunology, Brigham and Women's Hospital, Smith 652, One Jimmy Fund Way, Boston, MA, 02115, USA.
Anderson
P
P
D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000378:metabolism* / Q000628:therapy; D029721:Drosophila Proteins; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008562:Membrane Glycoproteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018121:Receptors, Cytokine / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051193:Toll-Like Receptors
D029721:Drosophila Proteins; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D051193:Toll-Like Receptors; D020928:Mitogen-Activated Protein Kinases