Anti-Allergic Action of Glucocorticoids: Comparison with Immunosuppressive and Anti-Inflammatory Effects
Glucocorticoid (GC) exhibits immunosuppressive and anti-inflammatory effects by suppressing the nuclear factor functions on T cells and monocytes / macrophages. GC exerts its effects by binding cytosolic GC receptor (GR) and antagonizes the transcription factors including AP-1, NF-κB and STATs, in both transcriptional regulation and upstream cross-talk with signaling molecules, resulting in the inhibition of target gene expression such as cytokines and other proteins, followed by the suppression of T cell activation and the production of inflammatory mediators. In addition, in anti-allergic actions of GC, one of the most important targets is mast cell. GC specifically inhibits the release of chemical mediators from mast cells. It also suppresses survival and activation of mast cells, at least in partial, overlapping with the suppressive mechanisms of T cell activation and monocytes / macrophages functions, by inhibiting the production of growth factors and inflammatory mediators, and suppressing the transcriptional induction of Th2-type cytokines, such as IL-4, -5, -10, -13 and TNF-α, chemokines and adhesion molecules, resulting in the suppression of immediate- and late-phase of allergic inflammation and remodeling. In this issue, we summarize the molecular mechanisms of GC to regulate the transcription factors, molecules regulated by GC and its action on the immune system in contrast with other agents, and also discuss the specific molecular targets of a possible drug design for allergy learned from the variable immunosuppressive and anti-inflammatory actions of GC.
Keywords: Glucocorticoid, Immunosuppression, Inflammation, Allergy, Mast cell, Transcription factor, Signal transduction
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