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Molecules 2016, 21(12), 1632; doi:10.3390/molecules21121632

Expression, Purification, and Characterization of Interleukin-11 Orthologues

1
Institute for Biological Instrumentation of the Russian Academy of Sciences, Institutskaya str., 7, Pushchino 142290, Moscow Region, Russia
2
Biocad, Lubuchany 142380, Moscow Region, Russia
3
Department of Molecular Medicine and USF Health Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
4
Antherix, Institutskaya str., 7, Pushchino 142290, Moscow Region, Russia
5
JSC R-Pharm, Berzarina str., 19/1, Moscow 123154, Russia
*
Authors to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 10 November 2016 / Revised: 22 November 2016 / Accepted: 24 November 2016 / Published: 29 November 2016
(This article belongs to the Section Natural Products)
View Full-Text   |   Download PDF [2490 KB, uploaded 29 November 2016]   |  

Abstract

Interleukin-11 (IL-11) is a multifunctional cytokine implicated in several normal and pathological processes. The decoding of IL-11 function and development of IL-11-targeted drugs dictate the use of laboratory animals and need of the better understanding of species specificity of IL-11 signaling. Here, we present a method for the recombinant interleukin-11 (rIL-11) production from the important model animals, mouse and macaque. The purified mouse and macaque rIL-11 interact with extracellular domain of human IL-11 receptor subunit α and activate STAT3 signaling in HEK293 cells co-expressing human IL-11 receptors with efficacies resembling those of human rIL-11. Hence, the evolutionary divergence does not impair IL-11 signaling. Furthermore, compared to human rIL-11 its macaque orthologue is 8-fold more effective STAT3 activator, which favors its use for treatment of thrombocytopenia as a potent substitute for human rIL-11. Compared to IL-6, IL-11 signaling exhibits lower species specificity, likely due to less conserved intrinsic disorder propensity within IL-6 orthologues. The developed express method for preparation of functionally active macaque/mouse rIL-11 samples is suited for exploration of the molecular mechanisms underlying IL-11 action and for development of the drug candidates for therapy of oncologic/hematologic/inflammatory diseases related to IL-11 signaling. View Full-Text
Keywords: cytokines; interleukin-11; ubiquitin; cloning; bacterial expression; protein-protein interaction; ligand-receptor interaction; STAT3 signaling cytokines; interleukin-11; ubiquitin; cloning; bacterial expression; protein-protein interaction; ligand-receptor interaction; STAT3 signaling
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Sokolov, A.S.; Kazakov, A.S.; Solovyev, V.V.; Ismailov, R.G.; Uversky, V.N.; Lapteva, Y.S.; Mikhailov, R.V.; Pavlova, E.V.; Terletskaya, I.O.; Ermolina, L.V.; Permyakov, S.E.; Permyakov, E.A. Expression, Purification, and Characterization of Interleukin-11 Orthologues. Molecules 2016, 21, 1632.

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