Expression, Purification, and Characterization of Interleukin-11 Orthologues
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. H...
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MDPI AG
2016-11-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/21/12/1632 |
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| author | Andrei S. Sokolov Alexei S. Kazakov Valery V. Solovyev Ramis G. Ismailov Vladimir N. Uversky Yulia S. Lapteva Roman V. Mikhailov Ekaterina V. Pavlova Iana O. Terletskaya Ludmila V. Ermolina Sergei E. Permyakov Eugene A. Permyakov |
| author_facet | Andrei S. Sokolov Alexei S. Kazakov Valery V. Solovyev Ramis G. Ismailov Vladimir N. Uversky Yulia S. Lapteva Roman V. Mikhailov Ekaterina V. Pavlova Iana O. Terletskaya Ludmila V. Ermolina Sergei E. Permyakov Eugene A. Permyakov |
| author_sort | Andrei S. Sokolov |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T22:41:49Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-13T22:41:49Z |
| publishDate | 2016-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-5ded3b8c93964163927ffb4183da0ae52022-12-22T02:26:35ZengMDPI AGMolecules1420-30492016-11-012112163210.3390/molecules21121632molecules21121632Expression, Purification, and Characterization of Interleukin-11 OrthologuesAndrei S. Sokolov0Alexei S. Kazakov1Valery V. Solovyev2Ramis G. Ismailov3Vladimir N. Uversky4Yulia S. Lapteva5Roman V. Mikhailov6Ekaterina V. Pavlova7Iana O. Terletskaya8Ludmila V. Ermolina9Sergei E. Permyakov10Eugene A. Permyakov11Institute for Biological Instrumentation of the Russian Academy of Sciences, Institutskaya str., 7, Pushchino 142290, Moscow Region, RussiaInstitute for Biological Instrumentation of the Russian Academy of Sciences, Institutskaya str., 7, Pushchino 142290, Moscow Region, RussiaBiocad, Lubuchany 142380, Moscow Region, RussiaInstitute for Biological Instrumentation of the Russian Academy of Sciences, Institutskaya str., 7, Pushchino 142290, Moscow Region, RussiaInstitute for Biological Instrumentation of the Russian Academy of Sciences, Institutskaya str., 7, Pushchino 142290, Moscow Region, RussiaInstitute for Biological Instrumentation of the Russian Academy of Sciences, Institutskaya str., 7, Pushchino 142290, Moscow Region, RussiaAntherix, Institutskaya str., 7, Pushchino 142290, Moscow Region, RussiaAntherix, Institutskaya str., 7, Pushchino 142290, Moscow Region, RussiaAntherix, Institutskaya str., 7, Pushchino 142290, Moscow Region, RussiaJSC R-Pharm, Berzarina str., 19/1, Moscow 123154, RussiaInstitute for Biological Instrumentation of the Russian Academy of Sciences, Institutskaya str., 7, Pushchino 142290, Moscow Region, RussiaInstitute for Biological Instrumentation of the Russian Academy of Sciences, Institutskaya str., 7, Pushchino 142290, Moscow Region, RussiaInterleukin-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.http://www.mdpi.com/1420-3049/21/12/1632cytokinesinterleukin-11ubiquitincloningbacterial expressionprotein-protein interactionligand-receptor interactionSTAT3 signaling |
| spellingShingle | Andrei S. Sokolov Alexei S. Kazakov Valery V. Solovyev Ramis G. Ismailov Vladimir N. Uversky Yulia S. Lapteva Roman V. Mikhailov Ekaterina V. Pavlova Iana O. Terletskaya Ludmila V. Ermolina Sergei E. Permyakov Eugene A. Permyakov Expression, Purification, and Characterization of Interleukin-11 Orthologues Molecules cytokines interleukin-11 ubiquitin cloning bacterial expression protein-protein interaction ligand-receptor interaction STAT3 signaling |
| title | Expression, Purification, and Characterization of Interleukin-11 Orthologues |
| title_full | Expression, Purification, and Characterization of Interleukin-11 Orthologues |
| title_fullStr | Expression, Purification, and Characterization of Interleukin-11 Orthologues |
| title_full_unstemmed | Expression, Purification, and Characterization of Interleukin-11 Orthologues |
| title_short | Expression, Purification, and Characterization of Interleukin-11 Orthologues |
| title_sort | expression purification and characterization of interleukin 11 orthologues |
| topic | cytokines interleukin-11 ubiquitin cloning bacterial expression protein-protein interaction ligand-receptor interaction STAT3 signaling |
| url | http://www.mdpi.com/1420-3049/21/12/1632 |
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