• Title, Summary, Keyword: Interleukin-18

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Insulin Resistance and Serum Levels of Interleukin-17 and Interleukin-18 in Normal Pregnancy

  • Jahromi, Abdolreza Sotoodeh;Shojaei, Mohammad;Ghobadifar, Mohamed Amin
    • IMMUNE NETWORK
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    • v.14 no.3
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    • pp.149-155
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    • 2014
  • We performed this study to evaluate the role of Interleukin-17 (IL-17) and Interleukin-18 (IL-18) in insulin resistance during normal pregnancy. This descriptive cross sectional study was carried out on 97 healthy pregnant women including 32, 25, and 40 individuals in the first, second, and third trimesters, respectively, and on 28 healthy non pregnant women between the autumn of 2012 and the spring of 2013. We analyzed the serum concentrations of IL-17 and IL-18 by using the enzyme linked immunosorbent assay (ELISA). Insulin resistance was measured by homeostasis model assessment of insulin resistance equation. No significant differences between the demographic data of the pregnant and non pregnant groups were observed. Insulin resistant in pregnant women was significantly higher than the controls (p=0.006). Serum IL-17 concentration was significantly different in non pregnant women and pregnant women in all gestational ages (p<0.05). Serum IL-18 level was significantly lower in subjects with first, second, and third trimesters of pregnancy in compared to non pregnant women (p<0.05). No significant correlations were found between serum IL-17 and IL-18 levels with insulin resistance (r=0.08, p=0.34 vs. r=0.01, p=0.91, respectively). Our data suggested that IL-17 and IL-18 do not appear to attribute greatly to pregnancy deduced insulin resistance during normal pregnancy.

The Interleukin-18 Promoter -607C>A Polymorphism Contributes to Nasopharyngeal Carcinoma Risk: Evidence from a Meta-analysis Including 1,886 Subjects

  • Guo, Xu-Guang;Xia, Yong
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7577-7581
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    • 2013
  • The interleukin-18 promoter -607C>A gene polymorphism may be related to nasopharyngeal carcinoma (NPC) risk but the results of individual studies remain conflicting. A meta-analysis including 1,886 subjects from five individual studies was therefore performed to provide a more accurate estimation. Pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were evaluated by fixed- or random-effects models. A significant relationship between interleukin-18 promoter -607C>A gene polymorphism and NPC was found in a dominant genetic model (OR: 1.351, 95% CI: 1.089-1.676, P=0.006, $P_{heterogeneity}$=0.904), a homozygote model (OR: 1.338, 95% CI: 1.023-1.751, P=0.034, $P_{heterogeneity}$=0.863), and a heterozygote model (OR: 1.357, 95% CI: 1.080-1.704, P=0.009, $P_{heterogeneity}$=0.824). No significant association was detected in either an allelic genetic model (OR: 1.077, 95% CI: 0.960-1.207, 0.207, $P_{heterogeneity}$=0.844) or a recessive genetic model (OR: 1.093, 95% CI: 0.878-1.361, P=0.425, $P_{heterogeneity}$=0.707). In conclusion, a significant association was found between interleukin-18 promoter -607C>A gene polymorphism and NPC risk. Individuals with the C allele of interleukin-18 promoter -607C>A gene polymorphism have a higher risk of NPC development.

Interleukin-18 Synergism with Interleukin-2 in Cytotoxicity and NKG2D Expression of Human Natural Killer Cells

  • Qi, Yuan-Ying;Lu, Chao;Ju, Ying;Wang, Zi-E;Li, Yuan-Tang;Shen, Ya-Juan;Lu, Zhi-Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.18
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    • pp.7857-7861
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    • 2014
  • Natural killer (NK) cells play an important role in anti-tumor immunity. Interleukin (IL)-18 is an immunoregulatory cytokine that induces potent NK cell-dependent anti-tumor responses when administrated with other cytokines. In this study, we explored the effects of combining IL-18 and IL-2 on NK cytotoxicity as well as expression levels of the NK cell receptor NKG2D in vitro. Freshly isolated PBMCs were incubated for 48 h with IL-18 and IL-2, then CD107a expression on $CD3^-CD56^+$ NK cells was determined by three-colour flow cytometry to evaluate the cytotoxicity of NK cells against human erythroleukemia K562 cells and human colon carcinoma HT29 cells. Flow cytometric analysis was also employed to determine NKG2D expression on NK cells. The combined use of IL-18 and IL-2 significantly increased CD107a expression on NK cells compared with using IL-18 or IL-2 alone, suggesting that the combination of these two cytokines exerted synergistic enhancement of NK cytotoxicity. IL-18 also enhanced NKG2D expression on NK cells when administered with IL-2. In addition, blockade of NKG2D signaling with NKG2D-blocking antibody attenuated the up-regulatory effect of combining IL-18 and IL-2 on NK cytolysis. Our data revealed that IL-18 synergized with IL-2 to dramatically enhance the cytolytic activity of human NK cells in a NKG2D-dependent manner. The results appear encouraging for the use of combined IL-18 and IL-2 in tumor immunotherapy.

Modulation of Humoral and Cell-Mediated Immunity Against Avian Influenza and Newcastle Disease Vaccines by Oral Administration of Salmonella enterica Serovar Typhimurium Expressing Chicken Interleukin-18

  • Rahman, Md Masudur;Uyangaa, Erdenebileg;Eo, Seong Kug
    • IMMUNE NETWORK
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    • v.13 no.1
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    • pp.34-41
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    • 2013
  • Interleukin-18 (IL-18) has been known to induce interferon-${\gamma}$ (IFN-${\gamma}$) production and promote Th1 immunity. Although mammalian IL-18 has been characterized in great detail, the properties and application of chicken IL-18 remain largely uninvestigated as of yet. In this study, we evaluated the immunomodulatory properties of Salmonella enterica serovar Typhimurium expressing chicken interleukin-18 (chIL-18) on immune responses induced by avian influenza (AI) and Newcastle disease (ND) vaccines. After oral administration of S. enterica serovar Typhimurium expressing chIL-18, chickens were vaccinated intramuscularly with the recommended dose of either inactivated AI H9N2 vaccine or ND (B1 strain) vaccine. Chickens receiving a primary vaccination were boosted using the same protocol 7 days later. Humoral and cell-mediated immune responses were evaluated in terms of HI antibody titers and proliferation and mRNA expression of IFN-${\gamma}$ and IL-4 of peripheral blood mononuclear cells (PBMC) in response to specific antigen stimulation. According to our results, oral administration of S. enterica serovar Typhimurium expressing chIL-18 induced enhanced humoral and Th1-biased cell-mediated immunity against AI and ND vaccines, compared to that of chickens received S. enterica serovar Typhimurium harboring empty vector. Therefore, we conclude that our proposed vaccination regimen using inactivated AI and ND viruses along with oral administration of S. enterica serovar Typhimurium expressing chIL-18 may provide a novel approach in protecting chicken from currently circulating AI and ND virus strains.

Production and Secretion of Human Interleukin-18 in Transgenic Tobacco Cell Suspension Culture

  • Sharma, Niti;Kim, Tae-Geum;Yang, Moon-Sik
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.11 no.2
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    • pp.154-159
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    • 2006
  • Interleukin-18 (IL-18), otherwise known as interferon-gamma-inducing factor (IGIF), is one of several well characterized and important cytokines that contribute to host defenses. The complementary DNA (cDNA) of mature human interleukin-18 gene (hIL-18) was fused with the signal peptide of the rice amylase 1A gene (Ramy1A) and introduced into the plant expression vector under the control of a duplicated CaMV 35S promoter. The recombinant plasmid was transformed into tobacco (Nicotiana tabacum L. cv Havana) using the Agrobacterium-mediated transformation method. The integration of the hlL-18 gene into the genome of transgenic tobacco plants was confirmed by polymerase chain reaction (PCR) amplification and its expression was observed in the suspension cells that were derived from the transgenic plant callus by using Northern blot analysis. The hlL-18 protein was detected in the extracts of the transgenic callus and in the medium of the transgenic tobacco suspension culture by using immunoblot analysis. Based upon enzyme-linked immunosorbant assay (ELISA) results, the expression level of the hlL-18 protein approximated $166{\mu}g/L$ in the suspension culture medium. Bioassay results from the induction of $interferon-{\gamma}$ from a KG-1 cell line indicated that the hlL-18 secreted into the suspension culture medium was bioactive.

Upregulation of IP-10(CXCL10) mRNA Expression by Interleukin-18

  • Kim, Hyo-Young;Kim, Hee-Sun
    • Yeungnam University Journal of Medicine
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    • v.24 no.1
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    • pp.67-78
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    • 2007
  • Background : Interleukin-18 (IL-18) is one of the principal inducers of interferon-${\gamma}$ (IFN-${\gamma}$) in lymphocytes. Materials and Methods : The effect of IL-18 on the expression of chemokine IP-10(CXCL10) mRNA in C57BL/6 mouse peritoneal macrophages was studied by using Northern blot analysis, enzyme linked immunosobent assay and electrophoretic mobility shift assay. Results : IL-18 was determined to exert no direct effect on the expression of IP-10(CXCL10) mRNA. However, IL-18 pretreatment was determined to play a cooperative role in the synergistic induction of LPS-induced IP-10(CXCL10) mRNA expression. The effect associated with IL-18 pretreatment with regard to the synergistic induction of LPS-induced IP-10 (CXCL10) mRNA expression was detected after 16 hr of IL-18 pretreatment, administered prior to LPS stimulation. The pattern of NF-${\kappa}B$ binding activity during IL-18 pretreatment with LPS stimulation was found to coincide with the expression of IP-10(CXCL10) mRNA. Conclusion : Although IL-18 alone exerts no direct effect on the expression of chemokine IP-10(CXCL10), a definite period of IL-18 pretreatment induces the synergistic expression of LPS-induced IP-10(CXCL10) mRNA. NF-${\kappa}B$ activation is a component of this synergistic effect of IL-18 pretreatment. These results provide useful information, which may facilitate the elucidation of the action mechanisms underlying IL-18 effect on the expression of IP-10(CXCL10) mRNA.

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Synergistic Effect of Interleukin-18 on the Expression of Lipopolysaccharide-Induced IP-10 (CXCL-10) mRNA in Mouse Peritoneal Macrophages

  • Kim, Hyo-Young;Kim, Jae-Ryong;Kim, Hee-Sun
    • Journal of Microbiology and Biotechnology
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    • v.16 no.10
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    • pp.1605-1612
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    • 2006
  • Interleukin (IL)-18, a member of the family of IL-l cytokine, is one of the principal inducers of $interferon-{\gamma}(IFN-{\gamma})$ in T lymphocytes and natural killer cells. The objective of the present study was to evaluate the effect of IL-18 on the expression of chemokine IP-10 (CXCL-10) mRNA in mouse peritoneal macrophages. IL-18 had very weak direct effect or synergistic effect with IL-12 on the expression of IP-10 mRNA in C57BL/6 mouse peritoneal macrophages. However, IL-18 pretreatment was found to playa cooperative role in the expression of lipopolysaccharide (LPS)-induced IP-10 mRNA. For the expression of LPS-induced IP-10 mRNA, the synergistic effect was detected after 16 h of IL-18 pretreatment prior to LPS stimulation. The expression level of CD14 in cells stimulated with LPS was not changed by IL-18 pretreatment, and the level of $IFN-{\gamma}$ production during IL-18 pretreatment plus LPS stimulation was barely discernible ($0.36{\pm}0.31pg/ml$). Namely, the synergistic effect of IL-18 pretreatment was not related to a change of LPS receptor, CD14 expression, and the production of $IFN-{\gamma}$ by the interaction between IL-18 and LPS. The synergistic effect of IL-18 pretreatment on the expression of LPS-induced IP-10 was related to not NF-kB but AP-1 activation, and associated with the extracellular signal-regulated kinase (ERK) pathway, one of the mitogen-activated protein kinase signaling pathways. These results provide useful information that may elucidate the mechanisms underlying the effect of IL-18 on the expression of IP-10 mRNA.

Association Between Interleukin-18 Level and Left Ventricular Mass Index in Hypertensive Patients

  • Ozbicer, Suleyman;Ulucam, Zekiye Melek
    • Korean Circulation Journal
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    • v.47 no.2
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    • pp.238-244
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    • 2017
  • Background and Objectives: In clinical trials, hypertensive patients tend to have higher interleukin-18 (IL-18) concentrations than normotensive groups, but the relationship between IL-18 and left ventricular hypertrophy (LVH), which is a marker of end-organ damage, is not well studied. We aimed to investigate the relationship between IL-18 and LVH in apparently healthy subjects free of clinically significant atherosclerotic disease. Subjects and Methods: We enrolled 198 subjects (102 women and 96 men) between May 2006 and March 2007, who were free of cardiovascular or immune diseases, but were suspected to have hypertension. Twenty-four-hour ambulatory blood pressure monitoring and two-dimensional echocardiography were performed. Lipid profiles, high-sensitivity CRP (hs-CRP), IL-18, and whole blood cell counts were measured for all subjects. Results: White blood cell count, hs-CRP, left ventricular mass, left ventricular mass index (LVMI), and IL-18 were higher in the hypertensive group than in the normotensive group (p=0.045, p=0.004, p<0.0001, p=0.001, and p=0.017 respectively). Twenty-four hour day and night systolic and diastolic blood pressure averages were positively correlated with IL-18 level in the entire study population. In multivariate regression analysis, left ventricular mass index and hs-CRP level were independently associated with IL-18 level in both the hypertensive group and the entire study population (${\beta}=0.154$, ${\beta}=0.149$ p=0.033, p=0.040 and ${\beta}=0.151$, ${\beta}=0.155$ p=0.036, p=0.032 respectively) Conclusion: We found that IL-18 level independently predicted LVMI in both the general population and in newly diagnosed hypertensive patients.

Inhibition of the Interleukin-11-STAT3 Axis Attenuates Hypoxia-Induced Migration and Invasion in MDA-MB-231 Breast Cancer Cells

  • Lim, Ji-Hong
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.5
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    • pp.391-396
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    • 2014
  • Although interleukin-11 (IL-11) has been reported to be elevated in hypoxic tumors and has been associated with a poor prognosis in various cancers, little is known about its precise role in promoting metastasis in hypoxic tumors. In the present study, the molecular mechanism underlying the effects of IL-11 on MDA-MB-231 breast cancer cells migration and invasion in relation to metastasis under hypoxic conditions has been defined. Inhibition of IL-11 expression or function using small interfering RNA (siRNA) or a neutralizing antibody attenuated hypoxic MDA-MB-231 breast cancer cell migration and invasion through down-regulation of matrix metalloproteinases (MMPs) and activation of epithelial-to-mesenchymal transition (EMT) related gene expression. In addition, hypoxia-induced IL-11 increased STAT3 phosphorylation and STAT3 knockdown suppressed hypoxic MDA-MB-231 breast cancer cell invasion due to reduced MMP levels and reprogrammed EMT-related gene expression. These results suggest that one of the hypoxic metastasis pathways and the regulation of this pathway could be a potential target for novel cancer therapeutics.

Immunotherapeutic Approach for Better Management of Cancer - Role of IL-18

  • Kuppala, Manohar Babu;Syed, Sunayana Begum;Bandaru, Srinivas;Varre, Sreedevi;Akka, Jyothy;Mundulru, Hema Prasad
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5353-5361
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    • 2012
  • Interleukin-18 (IL-18) is an immune-stimulatory cytokine with antitumor activity in preclinical models. It plays pivotal roles in linking inflammatory immune responses and tumor progression and is a useful candidate in gene therapy of lymphoma or lymphoid leukemia. A phase I study of recombinant human IL-18 (rhIL-18) in patients with advanced cancer concluded that rhIL-18 can be safely given in biologically active doses to patients with advanced cancer. Some viruses can induce the secretion of IL-18 for immune evasion. The individual cytokine activity might be potentiated or inhibited by combinations of cytokines. Here we focus on combinational effects of cytokines with IL-18 in cancer progression. IL-18 is an important non-invasive marker suspected of contributing to metastasis. Serum IL-18 may a useful biological marker as independent prognostic factor of survival. In this review we cover roles of IL-18 in immune evasion, metastasis and angiogenesis, applications for chemotherapy and prognostic or diagnostic significance.