Expression, Purification, and Characterization of Interleukin-11 Orthologues
AbstractInterleukin-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
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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.
Sokolov AS, Kazakov AS, Solovyev VV, Ismailov RG, Uversky VN, Lapteva YS, Mikhailov RV, Pavlova EV, Terletskaya IO, Ermolina LV, Permyakov SE, Permyakov EA. Expression, Purification, and Characterization of Interleukin-11 Orthologues. Molecules. 2016; 21(12):1632.Chicago/Turabian Style
Sokolov, Andrei S.; Kazakov, Alexei S.; Solovyev, Valery V.; Ismailov, Ramis G.; Uversky, Vladimir N.; Lapteva, Yulia S.; Mikhailov, Roman V.; Pavlova, Ekaterina V.; Terletskaya, Iana O.; Ermolina, Ludmila V.; Permyakov, Sergei E.; Permyakov, Eugene A. 2016. "Expression, Purification, and Characterization of Interleukin-11 Orthologues." Molecules 21, no. 12: 1632.
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