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.
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Authors | D P Kestler, K M Goldstein, S Agarwal, J E Fuhr, R Andrews, R E Hall |
Journal | American journal of hematology
(Am J Hematol)
Vol. 61
Issue 3
Pg. 169-77
(Jul 1999)
ISSN: 0361-8609 [Print] United States |
PMID | 10398309
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Copyright | Copyright 1999 Wiley-Liss, Inc. |
Chemical References |
- Interleukin-6
- Protein Isoforms
- RNA, Messenger
- Recombinant Proteins
- Muramidase
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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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