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

A. L. Benko, C. A. McAloose, P. M. Becker, D. Wright, T. Sunyer, Y. I. Kawasawa, N. J. Olsen, W. J. Kovacs

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)68-81
Number of pages14
JournalClinical and Experimental Immunology
Volume192
Issue number1
DOIs
StatePublished - Apr 2018

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Adrenocorticotropic Hormone
Glucocorticoids
B-Lymphocytes
Gene Expression
Messenger RNA
Injections
CD40 Ligand
Interleukin-4
RNA
Autoimmune Diseases
Up-Regulation
Down-Regulation
Gels
Cell Proliferation
Therapeutics
Genes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

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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 {\circledR} 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.",
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Repository corticotrophin injection exerts direct acute effects on human B cell gene expression distinct from the actions of glucocorticoids. / Benko, A. L.; McAloose, C. A.; Becker, P. M.; Wright, D.; Sunyer, T.; Kawasawa, Y. I.; Olsen, N. J.; Kovacs, W. J.

In: Clinical and Experimental Immunology, Vol. 192, No. 1, 04.2018, p. 68-81.

Research output: Contribution to journalArticle

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AU - Benko, A. L.

AU - McAloose, C. A.

AU - Becker, P. M.

AU - Wright, D.

AU - Sunyer, T.

AU - Kawasawa, Y. I.

AU - Olsen, N. J.

AU - Kovacs, W. J.

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AB - 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.

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