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.

An Interleukin-6 Receptor-dependent Molecular Switch Mediates Signal Transduction of the IL-27 Cytokine Subunit p28 (IL-30) via a gp130 Protein Receptor Homodimer

“…Because gp130 is ubiquitously expressed, the IL-6/sIL-6R complex can also stimulate cells that are nonresponsive to IL-6 alone (2). IL-6 remains the only example of a cytokine that in vivo uses both classic and transsignaling via the soluble IL-6R, even though IL-11 and ciliary neurotrophic factor have been shown to be able to mediate signals via the sIL-11R and soluble ciliary neuroptrophic factor receptor in vitro, respectively (25,26). The natural sgp130 protein and sgp130 designer proteins like sgp130Fc specifically block IL-6 trans-signaling without sterically affecting classic signaling because IL-6 alone has no measurable affinity to gp130.…”

Susceptibility of neuron-like cells derived from bovine Wharton’s jelly to bovine herpesvirus type 5 infections

“…The bWJ-MSCs were isolated and characterized as previously described [13] according to the Animal Care Committee at the University of São Paulo State, Brazil. The cell monolayers have been maintained in the laboratory of Animal Virology and Cell Culture since 2010 following standard procedures for seeding, freeze-thawing, and propagation.…”

“…These cells are easily obtained, proliferate rapidly in culture, are immunologically compatible, and represent fetal adnexa that is usually discarded [1,5]. MSCs have been previously isolated from dogs, sheep, horses [2,3,12], and recently bovine WJ-UC [13]. The WJ-UC cell structure is embryonic in origin and encloses the yolk sac, which is the source of the primordial germ cells and the first hematopoietic stem cells [5].…”

Designer Cytokine Hyper Interleukin 11 (H11) is a Megakaryopoietic Factor

“…The purified recombinant H11 was active in three different in vitro bio-assays: human hepatoma cells-HepG2-assay, B9 (hybridoma cells) bio-assay, and Ba/F3-gp130 bio-assay. H11 displayed much higher activity than IL-11 alone 15. Moreover, H11 demonstrated immune-adjuvant properties in the therapeutic whole cell cancer vaccine formulation in in vivo orthotopic renal cell cancer model 17.…”

“…We have constructed a novel designer cytokine Hyper IL-11 (H11), which is composed of full length of soluble IL-11 receptor (sIL-11R) and IL-11 15, 16. The fusion proteins are expected to be more stable and are needed in lower effective dose than separate components in supporting bioactivity.…”