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Hematopoietic differentiation activity of a recombinant human interleukin-6 (IL-6) isoform resulting from alternatively spliced deletion of the second exon.

Abstract
We have previously identified and cloned an alternatively spliced form of human interleukin-6 mRNA lacking exon II, which encodes amino acid residues known to be important in gp130-mediated signal transduction pathways. We expressed and purified the recombinant protein (rIL6-alt) resulting from this alternatively spliced mRNA and now report the initial characterization of its biologic activities with comparison to full length IL6 (rIL6-full). rIL6-alt was found to have 10(4) to 10(5) fold less activity in proliferation assays with 7TD1 murine plasmacytoma cells and did not competitively inhibit the stimulatory activity of rIL6-full. In addition, like rIL6-full, rIL6-alt had antiproliferative activity toward M1 murine myeloblast cells and was 10-200-fold less active than rIL6-full. In contrast, in assays with human HL60 promyelocytic leukemia cells, rIL6-alt had greater antiproliferative activity than rIL6-full and more strongly upregulated phagocytosis as well as surface expression of the differentiation antigen CD11b. rIL6-full and rIL6-alt upregulated the level of lysozyme mRNA in HL60 cells approximately equally. These findings suggest that IL6-alt, which lacks amino acid residues encoded by the second exon of the gene, is not a natural inhibitor of IL6-full but may be relatively tissue specific and may play a role in modulation of hematopoietic cell growth and differentiation.
AuthorsD P Kestler, K M Goldstein, S Agarwal, J E Fuhr, R Andrews, R E Hall
JournalAmerican journal of hematology (Am J Hematol) Vol. 61 Issue 3 Pg. 169-77 (Jul 1999) ISSN: 0361-8609 [Print] United States
PMID10398309 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
CopyrightCopyright 1999 Wiley-Liss, Inc.
Chemical References
  • Interleukin-6
  • Protein Isoforms
  • RNA, Messenger
  • Recombinant Proteins
  • Muramidase
Topics
  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Cell Differentiation (drug effects)
  • Cell Division (drug effects)
  • Cell Line
  • Cloning, Molecular
  • Exons
  • Gene Expression Regulation, Enzymologic (drug effects)
  • HL-60 Cells
  • Hematopoietic Stem Cells (cytology, drug effects)
  • Humans
  • Interleukin-6 (chemistry, genetics, pharmacology)
  • Mice
  • Molecular Sequence Data
  • Muramidase (genetics)
  • Protein Isoforms (chemistry, genetics, pharmacology)
  • RNA, Messenger (genetics)
  • Recombinant Proteins (chemistry, pharmacology)
  • Sequence Deletion
  • Signal Transduction

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