title: A designer hyper interleukin 11 (H11) is a biologically active cytokine.
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.
authors.affiliation: Department of Cancer Diagnostics and Immunology, Greater Poland Cancer Centre, 15 Garbary St, 61-866 Poznan, Poland. hanna.dams-kozlowska@wco.pl
authors.forename: Hanna
authors.initials: H
authors.lastname: Dams-Kozlowska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gryska
authors.forename: Eliza
authors.initials: E
authors.lastname: Kwiatkowska-Borowczyk
authors.forename: Dariusz
authors.initials: D
authors.lastname: Izycki
authors.forename: Stefan
authors.initials: S
authors.lastname: Rose-John
authors.forename: Andrzej
authors.initials: A
authors.lastname: Mackiewicz
mesh_terms: D000595:Amino Acid Sequence; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation; D003001:Cloning, Molecular; D050822:Cytokine Receptor gp130 / Q000378:metabolism; D005434:Flow Cytometry; D056945:Hep G2 Cells; D006801:Humans; D017370:Interleukin-11 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053703:Interleukin-11 Receptor alpha Subunit / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C508611:IL11 protein, human; C508600:IL6 protein, human; D017370:Interleukin-11; D053703:Interleukin-11 Receptor alpha Subunit; D015850:Interleukin-6; D011993:Recombinant Fusion Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050822:Cytokine Receptor gp130