Literature DB >> 9035138

I. A bioactive designer cytokine for human hematopoietic progenitor cell expansion.

M Fischer1, J Goldschmitt, C Peschel, J P Brakenhoff, K J Kallen, A Wollmer, J Grötzinger, S Rose-John.   

Abstract

Efficient expansion of hematopoietic progenitor cells requires, at least, the simultaneous stimulation of the receptors c-kit and gp130. While c-kit is activated by SCF; gp130, in cells which do not express sufficient amounts of IL-6R, can be activated by the complex of soluble IL-6R (sIL-6R) and IL-6. The therapeutic use of IL-6/sIL-6R, however, has been hampered by the high concentrations of the sIL-6R protein required. We have designed a fusion protein of sIL-6R and IL-6, linked by a flexible peptide chain, that was expressed to high levels. On gp130 expressing cells the fusion protein turned out to be fully active at 100 to 1,000-fold lower concentration than the combination of unlinked IL-6 and IL-6R. The fusion protein was used to effectively expand human hematopoietic progenitor cells ex vivo in a dose dependent fashion.

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Year:  1997        PMID: 9035138     DOI: 10.1038/nbt0297-142

Source DB:  PubMed          Journal:  Nat Biotechnol        ISSN: 1087-0156            Impact factor:   54.908


  154 in total

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Review 6.  Superagonism at G protein-coupled receptors and beyond.

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Review 8.  Interleukin-6: designing specific therapeutics for a complex cytokine.

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10.  The balance of interleukin (IL)-6, IL-6·soluble IL-6 receptor (sIL-6R), and IL-6·sIL-6R·sgp130 complexes allows simultaneous classic and trans-signaling.

Authors:  Paul Baran; Selina Hansen; Georg H Waetzig; Mohammad Akbarzadeh; Larissa Lamertz; Heinrich J Huber; M Reza Ahmadian; Jens M Moll; Jürgen Scheller
Journal:  J Biol Chem       Date:  2018-03-20       Impact factor: 5.157

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