Cytokines, Interleukin-11, Ubiquitin, Cloning, Bacterial Expression, Protein-protein Interaction, Ligand-receptor Interaction, STAT3 Signaling
Digital Object Identifier (DOI)
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.
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Citation / Publisher Attribution
Molecules, v. 21, issue 12, art. 1632
Scholar Commons Citation
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.; and Permyakov, Eugene A., "Expression, Purification, and Characterization of Interleukin-11 Orthologues" (2016). Molecular Medicine Faculty Publications. 880.