IL-27 Induced Apoptosis and Promoted Antitumor Cytokines Secretion in Human Monocytic Leukemic Cell Line U937.

Abstract 4418

IL-27 acts as a critical regulator in many pathological processes. Although IL-27 has been studied in many solid tumors, its effect on leukemia remains elusive. Here, we investigated expression of IL-27 receptor (WSX-1 and gp130) on bone marrow mononuclear cells (BM-MNCs) of 31 patients with acute myeloid leukemia (AML) and 8 controls (including patients with IDA, ITP and non-hematological diseases) by RT-PCR, exploring IL-27's property in malignant hematological diseases. In addition, we detected the secretion of antitumor cytokines, cell proliferation and apoptosis in human monocytic leukemic cellline (U397 cells) treated with IL-27. We found that expression rate of IL-27 receptor subunits in AML patients was significantly higher than those with benign hematological diseases, especially on the acute monocytic leukemia subtype (AML-M5 subtype). ELISA assay revealed that antitumor cytokines, including TNF-α and IL-12, were produced by IL-27 stimulated-U937 cells, with an optimal concentration of IL-27 at 60ng/mL and an optimal time at 24h. U937 cells' growth inhibition and apparent apoptosis was induced by IL-27 in a dose dependent manner. U937 cells displayed apparent apoptosis when treated by IL-27 over 40ng/ml. The apoptosis rate of U937 tumor cells reached peak level while the stimulation concentration was 100ng/ml. Hoechst 33258 staining also presented typical apoptotic bodies in U937 cells treated with IL-27. Based on the high expression of IL-27 receptor in BM-MNCs of AML patients, our data provided the first evidence that IL-27 functioned as an anti-leukemia cytokine, suppressing cell growth and inducing apoptosis, offering a new anticancer agent in leukemia therapy.