Expression of IL-18 and its receptor in human leukemia cells

Abstract 

The importance of IL-18, although clearly established in solid tumors, has not been fully elucidated in human hematopoietic neoplasms. Here we examined the mRNA and protein for IL-18 in eight human hematopoietic cell lines representing different lineages and neoplasms including leukemia, lymphoma and others. Our results revealed that IL-18 mRNA was expressed in these cells and that the corresponding protein was found in the cytoplasm. Seven of eight cell lines were also found to express two subunits of the IL-18 receptor (IL-18R) at varied levels. Furthermore, 29 out of 51 leukemia patients tested were observed to express IL-18R with 18/29 (62%) co-expression of both receptor and ligand. By blocking the IL-18 loop using specific antisense oligodeoxynucleotide (ASON) for IL-18 mRNA or anti-human IL-18R monoclonal antibody (McAbR), we were not able to demonstrate a marked inhibition on the most leukemic cell lines growth. Moreover, the potential proliferation in vitro of primary AML cells co-expressing IL-18 and its receptor was not significantly enhanced by recombinant human IL-18, suggesting that IL-18 is not apparently implicated in the proliferation of the leukemia cells via an autocrine loop. Additionally, we also found the effective modulating effect of M-CSF, IFN-α and TNF-α on IL-18R expression, implying an important in vivo effect of cytokines on IL-18-induced reaction. Moreover, the modulation of IL-18R expression was possibly irrelevant to IFN-γ secretion induced by these cytokines.

Abbreviations: AcPL, IL-1 receptor accessory protein-like protein, ALL, acute lymphocytic leukemia, AML, acute myeloid leukemia, ASON, antisense oligodeoxynucleotide, BMMC, bone marrow mononuclear cells, BSA, bovine serum albumin, CML, chronic myeloid leukemia, ELISA, enzyme-linked immunosorbent assay, FCS, fetal calf serum, GAPDH, glyceraldchyde 3-phosphate dehydrogenase, IFN-α, interferon-α, IL-1Rrp, IL-1R related protein, IRAK, IL-1R associated kinase, M-CSF, macrophage colony stimulating factor, IL-18, interleukin 18, IL-18R, IL-18 receptor, McAbR, anti-human IL-18R monoclonal antibody, PBMC, peripheral blood mononuclear cell, PI, propidium iodide, rhIL-18, recombinant human IL-18, RT-PCR, reverse transcriptase polymerase chain reaction, SON, sense oligodeoxynucleotides, TNF-α, tumor necrosis factor-α

Keywords: IL-18, IL-18 receptor, Autocrine, Modulation, Leukemia