Interleukin-18 directly activates T-bet expression and function via p38 mitogen-activated protein kinase and nuclear factor-κB in acute myeloid leukemia–derived predendritic KG-1 cells

Abstract

The leukemic cell line KG-1 was isolated from a patient with acute myeloid leukemia and is regarded a cellular model of human dendritic cell progenitors. The T helper type 1 cytokine interleukin (IL)-18 has been shown to induce the maturation of these cells towards a dendritic phenotype and, moreover, is able to mediate IFN; production in this model. Because T-box expressed in T cells (T-bet) is considered to be of paramount importance for dendritic cell function, the effects of IL-18 on this transcription factor have been investigated in the current study. Here, we show that activation of KG-1 cells by IL-18 induces T-bet mRNA and protein within 4 to 6 h of incubation. This hitherto unrecognized function of IL-18 was suppressed by the inhibition of p38 mitogen-activated protein kinase activity and nuclear factor-KB function.

IL-36γ/IL-1F9, an Innate T-bet Target in Myeloid Cells

“…Recently, we reported on robust induction of T-bet mRNA, protein, and biological activity (20) by IL-18 (IL-1F4) (21,22) in the predendritic acute myelogenous leukemia-derived cell line KG1 (23). Based on this experimental system we set out to identify novel T-bet-inducible genes by combining siRNA technology with genome-wide mRNA expression analysis.…”

Glycyrrhizic Acid-Mediated Subdual of Myeloid-Derived Suppressor Cells Induces Antileishmanial Immune Responses in a Susceptible Host

“…isceral leishmaniasis (VL), or kala-azar, caused by the protozoan parasite Leishmania donovani, is the most severe form of leishmaniasis (1)(2)(3). A major obstacle is imposed by immunosuppression during successful therapy against VL.…”

IL-18 gene expression pattern in exogenously treated AML cells

“…Similar to matrix metalloproteinases (MMP)-9 and -2, IL-18 is over-expressed in some hematologic malignancies such as AML, precluding a poor clinical outcome (4). Furthermore, IL-18 induces the maturation of these cells towards a dendritic phenotype (5) and is able to mediate interferon (IFN) gamma production (5).…”

“…IL-18 function(s) can be suppressed by the inhibition of p38 mitogen-activated protein kinase (MAPK) activity and nuclear factor-kappaB (NF-κB) function (5). Specific suppression of T-bet induction impairs the secretion of IFN gamma by KG-1 cells under the influence of IL-18, and therapeutic application of IL-18 has the potential to profoundly affect the biology of AML predendritic cells, such as KG-1 (5).…”