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.