Characterization And Roles Of IL-18 And Its Receptor In Leukemia Cells

Interleukin-18 (IL-18), previously known as interferon-γ (IFN-γ)-inducing factor, is a novel immnomodulatory cytokine, identified as a member of the IL-1 cytokine superfamily. However, IL-18 resembles the structurally unrelated cytokine IL-12. IL-18 spreads wide and plays multiple roles in vivo. In addition to strong IFN-γ inducing activity, IL-18 is able to induce production of Th1 cytokines such as GM-CSF, IL-2 and TNF-α to promote proliferation, development and differentiation of Th1 and activation of NK. In addition, IL-18 also induces production of Th2 cytokines such as IL-13 and/or IL-4 production by T/NK cells, mast cells and basophils. Therefore, IL-18 should be seen as a unique molecule that constitutes a critical link between innate and adaptive immunity. In particular, the clearance of intracellular bacteria, fungi and protozoa requires the induction of host-derived IFN-γ by IL-18. Involvement in the progression of pathogenicity in autoimmune diseases, chronic inflammatory diseases and allergic diseases was reported. Furthermore, in tumor models of experimental animals, IL-18 administration, IL-18 DNA vaccines and IL-18 gene- modified tumor cell vaccines all show curative effects. However, little is known about the characterization and roles of IL-18 and its receptor in leukemia cells.Recently, elevated IL-18 levels were found in serum from some leukemia patients, especially those with acute lymphocytic leukemia (ALL) and chronic myeloid leukemia (CML). In our previous work, we demonstrated that IL-18 was highly expressed in a human leukemia cell line J6-1, and demonstrated that pCl-18 significantly enhanced the cellular immune responses induced by M-CSFr DNA vaccine. In order to explore the characterization and roles of IL-18 and receptor in leukemia cells, we have completed the following work:1. Clinical studies on expression and significance of IL-18 in hematological diseases: By RT-PCR and Immunohistochemical method, we demonstrated that IL-18 was detected wide at elevated levels in the bone marrow of patients with hematological malignancies For the patients with leukemia or other malignant hematological disease (OMHD), the levels of IL-18 mRNA were clearly higher than that of normal donors. By contrast, there was no significant difference in the levels of transcription between patients with iron deficiency anemia (IDA) and normal controls, suggesting IL-18 might be a novel tumor related protein. DNA sequencing analysis revealed IL-18 cDNA derived from the AML sample selected shared 100% homologous with the...