Repository Corticotropin Injection exerts direct acute effects on human B cell gene expression distinct from the actions of glucocorticoids

Summary

Repository corticotropin injection (RCI, H.P Acthar® Gel) has been approved for use in the management of multiple autoimmune and inflammatory diseases for over a half-century, but its mechanism of action is not well understood. We used RNA –Seq methods to define RCI-regulated mRNAs in cultured human B cells under conditions of activation by IL4 and CD40 ligand. Following IL4/CD40L activation and RCI treatment we found up-regulation of 115 unique mRNA transcripts and downregulation of 80 unique mRNAs. The effect on these RNA levels was dose-dependent for RCI and was distinct from changes in mRNA expression induced by treatment with a potent synthetic glucocorticoid. RCI-downregulated mRNAs were observed to include a significant over-representation of genes critical for B cell proliferation under activating conditions. These data confirm that RCI exerts direct effects on human B cells to modulate mRNA expression in specific pathways of importance to B cell function and that, at the molecular level, the effects of RCI are distinct from those exerted by glucocorticoids. This article is protected by copyright. All rights reserved.