Post-transcriptional regulation of glucocorticoid function

Glucocorticoids (GCs) are corticosteroid hormones critically involved in the homeostatic control of stress and immune responses. Endogenous GCs generally tend to support the innate immune responses while inhibiting overexpressed adaptive immune responses. Synthetic GCs, given systemically or topically, are the first-line anti-inflammatory drug class prescribed in the treatment of the majority of chronic inflammatory and immune-mediated diseases. Regulation of gene transcription through the ligand-activated glucocorticoid receptor (GR) is the core mechanism of their anti-inflammatory action; however their regulatory function spans from early signaling-through non-genomic actions-to downstream post-translational modifications. The anti-inflammatory action of GCs is achieved also through post-transcriptional regulation (PTR) of gene expression, which modulates the rates of mRNA transport, decay and translation. The molecular mechanisms by which GC act on PTR are still ill-defined but studies aimed at their discovery have been increasing in the last decade, subsequent to definitive experimental evidences of the important pathogenic role of PTR in inflammatory responses. In this chapter we will review the growing data indicating that control of deregulated post-transcriptional pathways is a critical, yet underappreciated component of GCs' efficient anti-inflammatory action. A more detailed understanding of the molecular species and pathways by which GC regulate inflammation by post-transcriptional mechanisms may lead to novel anti-inflammatory strategies that could be pursued as a GC-independent therapeutic approach