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

J. A. Lust, D. F. Jelinek, K. A. Donovan, L. A. Frederick, B. K. Huntley, J. K. Braaten, N. J. Maihle

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Soluble receptors have been shown to be potent immunomodulators of their respective ligands. Since IL-6 is a central growth factor for myeloma cells, as sIL-6R may modulate IL-6 activity. We have previously reported a novel IL-6R mRNA from myeloma cells that exhibits a 94-nt deletion of the entire transmembrane domain from codons 356 (G-TG) to 387 (AG-G). The transmembrane domain deletion results in a shift in the translational reading frame with the insertion of 10 new amino acids followed by a stop codon. Sequence analysis shows the ligand-binding domain of the sIL-6R to be identical to that of the membrane-bound IL-6R up to the transmembrane domain deletion. The sIL-6R cDNA was expressed in QT-6 fibroblasts and PA-1 ovarian cells using the expression vector pCDM8. Supernates were immunoprecipitated with anti-IL-6R antibody and cells transfected with the sIL-6R cDNA produced a single band with a molecular weight of 50-55 kDa. This molecular weight corresponds to the size of the sIL-6R protein observed in normal human urine. Supernates were collected from mock or sIL-6R transfected PA-1 cells after 48 hours and assayed for their ability to stimulate or suppress the growth of an IL-6 dependent cell line, ANBL-6. Soluble IL-6R alone had no effect on the growth of the ANBL-6 cells. However, the growth of ANBL-6 cells by sIL-6R was potentiated in the presence of IL-6 and could be blocked by anti-IL-6 antibody. The above results suggest that, in the presence of IL-6, sIL-6R associates with gp130 leading to signal transduction and cell growth.

Original languageEnglish (US)
Pages (from-to)199-206
Number of pages8
JournalCurrent topics in microbiology and immunology
Volume194
StatePublished - Jan 1 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Microbiology
  • Immunology
  • Microbiology (medical)

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    Lust, J. A., Jelinek, D. F., Donovan, K. A., Frederick, L. A., Huntley, B. K., Braaten, J. K., & Maihle, N. J. (1994). Sequence, expression and function of an mRNA encoding a soluble form of the human interleukin-6 receptor (sIL-6R). Current topics in microbiology and immunology, 194, 199-206.