@article{a01e230f9f5646bdb5e62659f9ecd33f,
title = "Repository corticotrophin injection exerts direct acute effects on human B cell gene expression distinct from the actions of glucocorticoids",
abstract = " Repository corticotrophin injection (RCI, H.P Acthar {\textregistered} 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.",
author = "Benko, {A. L.} and McAloose, {C. A.} and Becker, {P. M.} and D. Wright and T. Sunyer and Kawasawa, {Y. I.} and Olsen, {N. J.} and Kovacs, {W. J.}",
note = "Funding Information: Our thanks to Ziaur Rahman MD, PhD for reading and commenting on the manuscript in preparation. A. L. B. participated in the design and performance of the experiments, the data analysis and the writing of the manuscript. C. A. McA. participated in the design and performance of the experiments, the data analysis and the writing of the manuscript. P. M. B. participated in the design of the experiments, the data analysis and the writing of the manuscript. D. W. participated in the design of the experiments, the data analysis and the writing of the manuscript. T. S. participated in the execution of the project, the data analysis and the writing of the manuscript. Y. I. K. participated in the design and performance of the experiments, the data analysis and the writing of the manuscript. N. J. O. participated in the design of the experiments, the data analysis and the writing of the manuscript. W. J. K. participated in the design of the experiments, the data analysis and the writing of the manuscript. We acknowledge the support of the Penn State Genome Sciences Core Facility. Core Facility services and instruments used in this project were funded, in part, under a grant with the Pennsylvania Department of Health using Tobacco Settlement Funds. The Department specifically disclaims responsibility for any analyses, interpretations or conclusions. These studies were supported by a research grant (to N. J. O.) from Mallinckrodt Pharmaceuticals. D. W., T. S. and P. B. are employees of Mallinckrodt Pharmaceuticals. The other authors had no competing interests. Publisher Copyright: {\textcopyright} 2017 British Society for Immunology",
year = "2018",
month = apr,
doi = "10.1111/cei.13089",
language = "English (US)",
volume = "192",
pages = "68--81",
journal = "Clinical and Experimental Immunology",
issn = "0009-9104",
publisher = "Wiley-Blackwell",
number = "1",
}