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Open AccessArticle

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
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Department of Molecular Medicine and USF Health Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
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Antherix, Institutskaya str., 7, Pushchino 142290, Moscow Region, Russia
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JSC R-Pharm, Berzarina str., 19/1, Moscow 123154, Russia
*
Authors to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Molecules 2016, 21(12), 1632; https://doi.org/10.3390/molecules21121632
Received: 10 November 2016 / Revised: 22 November 2016 / Accepted: 24 November 2016 / Published: 29 November 2016
(This article belongs to the Section Natural Products Chemistry)
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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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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