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Inflammation is one of the biggest challenges in current medicine. Glucocorticoid-based therapy is still the most commonly used treatment to combat chronic and acute inflammation. However, as this treatment is burdened with a detrimental side effect profile and the occurrence of glucocorticoid resistance, research efforts are focused on characterizing the anti-inflammatory mechanisms of glucocorticoids and developing new therapeutic strategies to fight inflammation. In this book, focus is put on the effects of the glucocorticoid receptor on NF-kB and NF- B-driven gene expression. The transcription factor NF- B is namely key to the onset and propagation of inflammation. Special attention is also given to the effects of glucocorticoids on the kinase MSK1 and the associated chromatin and NF- B modulations. In a second chapter, we explore alternative glucocorticoid receptor function via the selective agonist Compound A. Further unravelling the underlying mechanism of how glucocorticoids mediate anti-inflammatory gene repression is a very important issue for molecular researchers, biochemists, medical doctors and specialists, pharmaceutical companies, and product managers.