The role of interleukin-18 and interleukin-18 receptor in predominant Th1 immune response of patients with immune thrombocytopenia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the role of interleukin (IL)-18 and IL-18 receptor (IL-18R) in the predominant Th1 type cytokine response in patients with immune thrombocytopenia (ITP).</p><p><b>METHODS</b>Fifteen patients with active phase ITP, eighteen in remission and thirteen healthy controls were enrolled in this study. T-bet and GATA-3 mRNA levels in peripheral blood mononucleated cells (PBMNC) were measured by reverse transcriptase polymerase chain reaction (RT-PCR); the plasma IL-18 level by enzyme linked immunosorbent assay (ELISA), the expression of IL-18R on CD3(+) lymphocytes and total lymphocytes by flow cytometry(FCM).</p><p><b>RESULTS</b>The T-bet mRNA levels in patients with active phase ITP was 3.572 fold as much as that in the controls (P < 0.05), while the GATA-3 mRNA levels were 0.378 fold of that in controls (P < 0.05). The levels of plasma IL-18 and IL-18R on CD3(+) lymphocytes were significantly increased in active phase ITP than in remission phase and controls. There was no difference in ratio of T-bet/GATA-3 between remitted ITP and controls and so was for T-bet mRNA, GATA-3 mRNA, plasma IL-18 and IL-18R on CD3(+) lymphocytes.</p><p><b>CONCLUSION</b>ITP as a disease of Th1-dominant response there is an unbalance between T-bet and GATA-3 in its active phase; IL-18 and IL-18R being upregulated.</p>

Upregulation of Reactive Oxygen Species and Resistance to Fas-mediated Apoptosis in Cervical Cancer Cell Lines Transfected with the IL-18 Receptor / 대한진단검사의학회지

BACKGROUND: The fas (CD95/Apo-1)/Fas ligand (FasL) system is reported to be involved in the suppression and stimulation of immune responses, and the reactive oxygen species (ROS) play a key role in the mechanism for resisting Fas-induced apoptosis of tumor cells. In this work, we investigated the effect of endogenous interleukin (IL)-18 on the regulation of immune related factors such as Fas/Fas ligand and intercellular adhesion molecules (ICAM), and of the ROS level in IL-18 receptor (IL-18R) transfected C-33A cells. METHODS: The cervical cancer cell line C-33A was transfected with IL-18R (C-33A/IL-18R). For the detection of pro-inflammatory cytokines in C-33A/IL-18R, reverse-transcriptase (RT) polymerase chain reaction (PCR), in situ enzyme-linked immunosorbent assay (ELISA), Western blot, and Northern blot analyses were performed. The level of p53 was determined by Western blot. Intracellular ROS, ICAM-1, FasL, and apoptosis in C-33A/IL-18R were measured by flow cytometry. RESULTS: In situ ELISA and RT-PCR showed that, among pro-inflammatory cytokines, IL-18 was induced in C-33A/IL-18R whereas there appeared no induction of the IL-1alpha, IL-1beta, tumor necrosis factor (TNF)-alpha, and IL-6. IL-18R transfection showed a slight enhancement of the Fas via upregulation of intracellular ROS and IL-18 in C-33A cells whereas there was no effect on the expression of p53, ICAM-1 and FasL. However, treatment with the agonistic anti-Fas antibody showed that the enhanced surface Fas was not functional or was not enough to induce apoptosis and the C-33A/IL-18R cells escaped still resistant to Fas-mediated apoptosis. CONCLUSIONS: IL-18R transfection induced IL-18 expression and enhanced ROS and Fas expression in C-33A cells. These results show that C-33A/IL-18R cells escaped from immunuosurveillance by failure to express ICAM-1 adhesion molecules and Fas ligand, and are resistant to Fas-mediated apoptosis.