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

BMC Biotechnol. 2012 Mar 21;12:8. doi: 10.1186/1472-6750-12-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Differentiation / physiology
  • Cell Line
  • Cell Proliferation
  • Cloning, Molecular
  • Cytokine Receptor gp130 / metabolism
  • Flow Cytometry
  • Hep G2 Cells
  • Humans
  • Interleukin-11 / chemistry
  • Interleukin-11 / genetics
  • Interleukin-11 / metabolism*
  • Interleukin-11 Receptor alpha Subunit / chemistry
  • Interleukin-11 Receptor alpha Subunit / genetics
  • Interleukin-11 Receptor alpha Subunit / metabolism*
  • Interleukin-6 / metabolism
  • Molecular Sequence Data
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism*
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction

Substances

  • IL11 protein, human
  • IL6 protein, human
  • Interleukin-11
  • Interleukin-11 Receptor alpha Subunit
  • Interleukin-6
  • Recombinant Fusion Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Cytokine Receptor gp130