Repository corticotrophin injection exerts direct acute effects on human B cell gene expression distinct from the actions of glucocorticoids. (12th January 2018)

• Record Type: Journal Article
• Authors: Benko, A L; McAloose, C A; Becker, P M; Wright, D; Sunyer, T; Kawasawa, Y I; Olsen, N J; Kovacs, W J
• Is Part Of: Clinical and experimental immunology. Volume 192:Number 1(2018:Apr.)
• Page Start: 68
• Page End: 81
• Publication Date: 2018-01-12
• Subjects: antibodies -- B cell -- gene regulation -- human -- neuroimmunology; Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.13089
• Languages: English
• ISSNs: 0009-9104

Abstract

Summary: Repository corticotrophin injection (RCI, H.P Acthar ® gel) has been approved for use in the management of multiple autoimmune and inflammatory diseases for more than 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 interleukin (IL)-4 and CD40 ligand. Following IL-4/CD40L activation and RCI treatment we found up-regulation of 115 unique mRNA transcripts and down-regulation 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 down-regulated 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. Graphical Abstract: