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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
Author(s) -
Kestler Daniel P.,
Goldstein Keith M.,
Agarwal Sujata,
Fuhr Joseph E.,
Andrews Richard,
Hall Robert E.
Publication year - 1999
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/(sici)1096-8652(199907)61:3<169::aid-ajh3>3.0.co;2-9
Subject(s) - microbiology and biotechnology , biology , hl60 , exon , haematopoiesis , cellular differentiation , alternative splicing , signal peptide , leukemia , recombinant dna , stem cell , gene , biochemistry , immunology
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. Am. J. Hematol. 61:169–177, 1999. © 1999 Wiley‐Liss, Inc.