Mapracorat, a selective glucocorticoid receptor agonist, upregulates RelB, an anti-inflammatory nuclear factor-kappaB protein, in human ocular cells.

摘要: Selective glucocorticoid receptor agonists (SEGRAs) are a new class of compounds under clinical evaluation for treatment ocular inflammation. Widely prescribed therapeutics, such as glucocorticoids, effective at reducing inflammation, but their long term use predisposes to undesirable side effects. The purpose this study was investigate novel SEGRA, mapracorat (BOL-303242-X), and the differences in mapracorat's mechanism action compared with traditional steroids (i.e. dexamethasone). Keratocytes from three different humans were cultured treated or dexamethasone, without strong provoking agent, interleukin (IL)-1β. effects dexamethasone determined by measuring protein levels (Western blotting) DNA binding (ELISA) two nuclear factor-kappaB (NF-κB) family members, RelA RelB. Cytokine production IL-6, IL-8, prostaglandin E2 (PGE2)) characterized immunoassay. Our findings reveal mechanistic between steroid therapies. Mapracorat showed partial attenuation classical NF-κB pathway, consistent steroids. However, uniquely potentiated anti-inflammatory through rapid upregulation RelB, an member alternative pathway. potently inhibits inflammation in vitro is promising inflammatory disease. acts, part, via RelB