Signaling pathways in rheumatoid arthritis

Signaling pathways orchestrate the inflammatory response by regulating various cellular functions such as programmed cell death, cell differentiation and proliferation or secretion of signaling molecules. They are classically activated by ligand engagement of surface receptors but increasing evidence suggests that intracellular proteins can also detect danger signals. Protection from pathogens, chemical or physical injury, or neoplasia relies on a tightly regulated activation of these mechanisms. The same signaling cascades sometimes escape from normal controls and increase the production of cytokines, proteases, growth factors and chemokines up to harmful levels, leading to an autodestructive process as seen in rheumatoid arthritis. Mapping the hierarchy of these pathways identifies which specific targets can be inhibited to safely reduce the levels of inflammatory molecules and reset the homeostasis of the organism.