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Open Access Research article

A designer hyper interleukin 11 (H11) is a biologically active cytokine

Hanna Dams-Kozlowska12*, Katarzyna Gryska2, Eliza Kwiatkowska-Borowczyk12, Dariusz Izycki2, Stefan Rose-John3 and Andrzej Mackiewicz12

Author Affiliations

1 Department of Cancer Diagnostics and Immunology, Greater Poland Cancer Centre, 15 Garbary St, 61-866 Poznan, Poland

2 Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan, Poland

3 Department of Biochemistry, Christian-Albrechts-University, Kiel, Germany

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BMC Biotechnology 2012, 12:8  doi:10.1186/1472-6750-12-8

Published: 21 March 2012

Abstract

Background

Interleukin 11 (IL-11) is a pleiotropic cytokine with anti-apoptotic, anti-inflammatory and hematopoietic potential. The IL-11 activity is determined by the expression of the IL-11R receptor alpha (IL-11Rα) and the signal transducing subunit β (gp130) on the cell membrane. A recombinant soluble form of the IL-11Rα (sIL-11Rα) in combination with IL-11 acts as an agonist on cells expressing the gp130 molecule. We constructed a designer cytokine Hyper IL-11 (H11), which is exclusively composed of naturally existing components. It contains the full length sIL-11Rα connected with the mature IL-11 protein using their natural sequences only. Such a construct has two major advantages: (i) its components are as close as possible to the natural forms of both proteins and (ii) it lacks an artificial linker what should avoid induction of antibody production.

Results

The H11 construct was generated, the protein was produced in a baculovirus expression system and was then purified by using ion exchange chromatography. The H11 protein displayed activity in three independent bioassays, (i) it induced acute phase proteins production in HepG2 cells expressing IL-11, IL-11Rα and gp130, (ii) it stimulated the proliferation of B9 cells (cells expressing IL-11Rα and gp130) and (iii) proliferation of Baf/3-gp130 cells (cells not expressing IL-11 and IL-11Rα but gp130). Moreover, the preliminary data indicated that H11 was functionally distinct from Hyper-IL-6, a molecule which utilizes the same homodimer of signal transducing receptor (gp130).

Conclusions

The biologically active H11 may be potentially useful for treatment of thrombocytopenia, infertility, multiple sclerosis, cardiovascular diseases or inflammatory disorders.

Keywords:
IL-11; sIL-11Rα; Hyper-IL11; Fusion protein; gp130 targeting; Hypercytokine