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Sequence, expression and function of an mRNA encoding a soluble form of the human interleukin-6 receptor (sIL-6R)

J A Lust1, D F Jelinek, K A Donovan

  • 1Department of Laboratory Medicine, Mayo Clinic, Rochester, MN.

Current Topics in Microbiology and Immunology
|January 1, 1995
PubMed

Insights

A novel soluble interleukin-6 receptor (sIL-6R) from myeloma cells modulates IL-6 activity. In the presence of IL-6, sIL-6R promotes myeloma cell growth by associating with gp130.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cancer Research

Background:

  • Soluble receptors are key immunomodulators.
  • Interleukin-6 (IL-6) is a critical growth factor for myeloma cells.
  • A novel IL-6 receptor (IL-6R) mRNA with a transmembrane domain deletion was identified in myeloma cells.

Purpose of the Study:

  • To investigate the functional role of the novel soluble IL-6 receptor (sIL-6R) in modulating IL-6 activity.
  • To determine if sIL-6R influences the growth of IL-6 dependent myeloma cells.

Main Methods:

  • Expression of sIL-6R cDNA in QT-6 fibroblasts and PA-1 ovarian cells.
  • Immunoprecipitation of sIL-6R from cell supernatants.
  • Assay of sIL-6R's effect on the growth of the IL-6 dependent cell line ANBL-6 in the presence and absence of IL-6.

Main Results:

  • Transfected cells produced a 50-55 kDa sIL-6R protein, consistent with urinary sIL-6R.
  • Soluble IL-6R alone did not affect ANBL-6 cell growth.
  • sIL-6R potentiated IL-6-induced ANBL-6 cell growth, which was blocked by anti-IL-6 antibody.

Conclusions:

  • The novel sIL-6R functions as an immunomodulator of IL-6 activity.
  • In the presence of IL-6, sIL-6R associates with gp130, leading to signal transduction and promoting myeloma cell growth.

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