Owing to their strong anti-inflammatory properties, glucocorticoids (GCs) are often used for the treatment of inflammatory and autoimmune diseases. However, despite the success of GC therapy, the anti-inflammatory mechanism is still largely unknown, particularly the relative role of the GR transcriptional actions. In addition, millions of patients display diverse side-effects and/or a lack of response to GCs, referred to as glucocorticoid resistance. There is an urgent need for more efficacious GC therapy. Therefore, research in our lab is focused on obtaining new insights into the mechanisms of GC-mediated actions.
Part of the anti-inflammatory actions of GCs can be explained by the induction of genes with potent anti-inflammatory effects. In addition to protein-coding genes, many non-coding transcripts (ncRNAs), such as microRNAs and long non-coding RNAs, are transcribed from the mammalian genome. We aim to identify in this project which ncRNAs show a different expression by GCs. As we speculate that these ncRNAs might be involved in the anti-inflammatory actions of GCs, we will investigate the contribution of selected ncRNAs in the protection of GCs against TNF-induced inflammation. Therefore, we will perform overexpression and knockdown studies.
In conclusion, we are addressing the problem of the unresolved anti-inflammatory actions of GCs, focusing on the GC-mediated transcriptional induction of ncRNAs. Hence, we hope to establish more efficient GC-based therapies.