Primer: signal transduction in rheumatic disease--a clinician's guide.
Signaling pathways enable cells to respond and adapt to environmental stimuli. For instance, extracellular ligands, such as proinflammatory cytokines or pathogen components, bind receptors on the surface of cells that trigger downstream signaling cascades driven by enzymes called kinases. Ultimately, kinases activate transcription factors that bind to DNA and alter the expression of target genes, the products of which allow the cell to respond to the initial stimulus. A variety of chronic inflammatory diseases are associated with altered cellular signaling. Some of the signal cascades that are involved in inflammation and autoimmunity include those mediated by mitogen-activated protein kinases, nuclear factor-kappaB, interferon regulatory factor and Toll-like receptors, NOD-like receptors and the inflammasome, and phosphatidylinositol-3-kinases. Understanding these intracellular pathways might lead to new approaches to the treatment of inflammatory disease, including the use of orally bioavailable small molecules that regulate cytokine function and production.
Sweeney
Susan E
SE
Division of Rheumatology, Allergy and Immunology, University of California San Diego, Department of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0656, USA. ssweeney@ucsd.edu
Firestein
Gary S
GS
D006801:Humans; D007249:Inflammation / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000378:metabolism; D007596:Joints / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D012216:Rheumatic Diseases / Q000188:drug therapy / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D051193:Toll-Like Receptors / Q000378:metabolism; D014158:Transcription, Genetic
D050835:Interferon Regulatory Factors; D016328:NF-kappa B; D051193:Toll-Like Receptors; D019869:Phosphatidylinositol 3-Kinases