• Title/Summary/Keyword: interleukin-12

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Antitumor Activity of Lentivirus-mediated Interleukin -12 Gene Modified Dendritic Cells in Human Lung Cancer in Vitro

  • Ali, Hassan Abdellah Ahmed;Di, Jun;Mei, Wu;Zhang, Yu-Cheng;Li, Yi;Du, Zhen-Wu;Zhang, Gui-Zhen
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.611-616
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    • 2014
  • Objectives: Dendritic cell (DC)-based tumor immunotherapy needs an immunogenic tumor associated antigen (TAA) and an effective approach for its presentation to lymphocytes. In this study we explored whether transduction of DCs with lentiviruses (LVs) expressing the human interleukin-12 gene could stimulate antigen-specific cytotoxic T cells (CTLs) against human lung cancer cells in vitro. Methods: Peripheral blood monocyte-derived DCs were transduced with a lentiviral vector encoding human IL-12 gene (LV-12). The anticipated target of the human IL-12 gene was detected by RT-PCR. The concentration of IL-12 in the culture supernatant of DCs was measured by ELISA.Transduction efficiencies and CD83 phenotypes of DCs were assessed by flow cytometry. DCs were pulsed with tumor antigen of lung cancer cells (DC+Ag) and transduced with LV-12 (DC-LV-12+Ag). Stimulation of T lymphocyte proliferation by DCs and activation of cytotoxic T-lymphocytes (CTL) stimulated by LV-12 transduced DCs pulsed with tumor antigen against A549 lung cancer cells were assessed with methyl thiazolyltetrazolium (MTT). Results: A recombinant lentivirus expressing the IL-12 gene was successfully constructed. DC transduced with LV-12 produced higher levels of IL-12 and expressed higher levels of CD83 than non-transduced. The DC modified by interleukin -12 gene and pulsed with tumor antigen demonstrated good stimulation of lymphocyte proliferation, induction of antigen-specific cytotoxic T lymphocytes and antitumor effects. Conclusions: Dendritic cells transduced with a lentivirus-mediated interleukin-12 gene have an enhanced ability to kill lung cancer cells through promoting T lymphocyte proliferation and cytotoxicity.

A study on the effects of herbal acupuncture with Liriopis Tuber extract on airway inflammation in the mouse induced with bronchial asthma

  • Park, Young-Whan;Park, Hee-Soo
    • Journal of Pharmacopuncture
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    • v.4 no.1
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    • pp.105-121
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    • 2001
  • Objectives: Herbal acupuncture has been administered with Liriopis Tuber extract on the point of BL 13 (Pyesu) to treat bronchial asthma and a certain degree of clinical benefits have been observed but lacking scientific substantiation. Methods: The present report describes on Th1 cytokine (Interleukin-2, Interferon-gamma), Th2 cytokine, (Interleukin-4, Interleukin-5), and IL-12 in bronchoalveolar lavage fluid (ELISA). Five groups were devised to study the effects of herbal acupuncture with Liriopis Tuber extract at BL 13 (Pyesu) for airway inflammation in the mouse model with bronchial asthma. Results shows that herbal acupuncture with Liriopis Tuber extract at BL 13 increased Th1 cytokine (Interleukin-2) in allergic sensitization and allergic challenge, and decreased Th2 cytokine (Interleukin-2, Interleukin-5) in allergic sensitization.

Changes of Interleukin-12 and Transforming Growth Factor Beta 1 before and after Antipsychotic Treatments in Schizophrenic Patients (정신분열병 환자에서 Interleukin-12와 Transforming Growth Factor Beta 1의 치료 전후의 변화)

  • Kim, Sung-Jae;Lee, Bun-Hee;Kim, Yong-Ku
    • Korean Journal of Biological Psychiatry
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    • v.12 no.2
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    • pp.143-150
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    • 2005
  • Background:Several reports have suggested that cytokine alterations could be related to the pathophysiology of schizophrenia. In this study, we measured plasma level of interleukin-12(IL-12), a proinflammatory T helper 1(Th1) cytokine and transforming growth factor-${\beta}1$(TGF-${\beta}1$), an anti-inflammatory Th3 cytokine before and after antipsychotic treatment in schizophrenic patients. Methods:The plasma concentrations of IL-12 and TGF-${\beta}1$ were measured by using quantitative ELISA in 23 schizophrenic patients and 31 normal controls at admission and 8 weeks later. The psychopathology was measured by Brief Psychiatric Rating Scale(BPRS). Results:IL-12 and TGF-${\beta}1$ levels were significantly higher in schizophrenic patients than in controls before treatment. At the 8 week of treatment, the TGF-${\beta}1$ levels returned to control values, while IL-12 levels were not significantly changed. There were no significant correlations between the changes of BPRS scores and the changes of IL-12 or TGF-${\beta}1$ levels in schizophrenic patients. Conclusion:Cytokine abnormalities in schizophrenia might be involved in the pathophysiology of the illness. It is possible that TGF-${\beta}1$ plays an important role in the schizophrenia.

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The Change of Interleukin-12 and Transforming Growth Factor-${\beta}$1 Level in Manic Patients after Treatment (양극성장애에서 Interleukin-12와 Transforming Growth Factor-${\beta}$1의 치료 전후의 변화)

  • Choi, Hyun-Seok;Kim, Yong-Ku
    • Korean Journal of Biological Psychiatry
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    • v.13 no.1
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    • pp.32-37
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    • 2006
  • Background : Several studies have suggested that alterations of cytokine level could be related to the pathophysiology of bipolar disorder. In this study, we measured plasma level of Interleukin-12(IL-12), a pro-inflammatory cytokine and transforming growth factor-${\beta}$1(TGF-${\beta}$1), an anti-inflammatory cytokine before and after treatment in acute manic patients. Methods : The plasma concentrations of IL-12 and TGF-${\beta}$1 were measured using quantitative ELISA in 18 bipolar disorder patients and 25 normal controls at admission and 6 weeks later. The psychopathology was measured by Brief Psychiatric Rating Scale(BPRS) and Young Mania Rating Scale(YMRS). Results : IL-12 levels were significantly higher in bipolar manic patients than in controls before treatment. Following the 6-week treatment, the IL-12 level was decreased than before treatment, but sustained still higher level than normal control. TGF-${\beta}$1 level was not significant different between manic patients and normal controls before treatment, but was increased after treatment comparing with before treatment in bipolar patients. The ratio of IL-12 and TGF-${\beta}$1 was significantly decreased after treatment. Conclusion : Cytokine abnormalities in bipolar disorder might be involved in the pathophysiology of the illness. It is possible that TGF-${\beta}$1 plays an important role in the regulation of immunological imbalance in bipolar disorder.

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Inhibitory Effects of Piperine on the Production of Nitric Oxide, Interleukin-10 and Interleukine-12 in Murine Peritoneal Macrophages (복강 대식세포에서 피페린의 일산화질소, 인테루킨-10과 인테루킨-12의 억제 효과)

  • Bae, Gi-Sang;Lee, Ju-Sung;Sung, Kang-Keyng;Park, Sung-Joo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.2
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    • pp.452-456
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    • 2009
  • The purpose of this study was to investigate the anti-inflammatory effects and cellular mechanism of piperine on murine peritoneal macrophages. To evaluate the effects of piperine, we examined the production of nitric oxide (NO), interleukin (IL)-10 and IL-12. To investigate inhibitory mechanism of piperine, we examined the MAPKs and Ik-Ba in murine peritoneal macrophages, Piperine itself does not have any cytotoxic effect and reduced lipopolysaccharid (LPS), Poly(I:C), CpG-ODN -induced production of NO, IL-10 and IL-12 in peritoneal macrophages. Piperine inhibited the activation of extracelluar signal-regulated kinase (ERK 1/2) and c-Jun NH2-terminal kinase (JNK 1/2) not the activation of p38 and the degradation of inhibitory kappa B a (Ik-Ba) in the LPS-stimulated murine peritoneal macrophages.ln conclusion, Piperine down-regulated LPS-induced production of NO, IL-10 and IL-12, which could provide a clinical basis for anti-inflammatory properties of piperine.

The effect of Substance P on the secretion of Interleukin-8 and MCP (Monocyte Chemoattractant Protein)-1 from the Human Dental Pulp Cells (치수세포의 Substance P 자극 시 Interleukin-8과 Monocyte chemattractant protein-1의 분비에 관한 연구)

  • Park, Sang-Hyuk
    • Restorative Dentistry and Endodontics
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    • v.28 no.5
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    • pp.409-418
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    • 2003
  • 본 연구는 치수 염증 시 IL-8과 MCP-1 분비에서 neuropeptide의 역할에 대해 관찰하고자 발거된 건전한 치아를 수직 파절시켜 치수조직을 채취하여 배양된 치수세포 및 혈관내피세포(ECV 304세포)를 각기 다른 농도의 Substance P(SP)로 12시간 자극하였고, 24시간 동안 4시간 간격으로 시간대별로 자극하였으며, 또 치수세포를 Calcitonin gene-related peptide (CGRP)로 12시간 자극하였다. 이들 세포를 SP길항제 (Spantide)로 15분간 차단한 후 SP로 12시간 재 자극하였으며, SP와 CGRP혼합액을 12시간 자극하였다. 상기의 실험 후 부유물로 ELISA를 시행하여 IL-8과 MCP-1의 분비 량을 측정하였다. 치수세포는 SP로 자극 시 IL-8이 현저히 증가한 반면, CGRP는 효과가 없었으며, SP와 CGRP를 혼합자극 시 시너지 효과 또한 없었고, Spantide는 치수세포의 IL-8과 MCP-1의 분비를 차단시켰다. 치수세포를 SP로 24시간 동안 4시간 간격으로 자극 시 8시간 후 최대의 IL-8은 분비량 나타내었으며, 8시간과 12시간 사이에서 최대의 MCP-1 분비량을 나타내었다. ECV 304세포를 SP로 자극 시 IL-8과 MCP-1 분비량이 미약하게 증가하였으며, Spantide는 ECV 304세포의 IL-8과 MCP-1 분비를 억제시켰다.

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.

Protective Effect of Decursinol on Mouse Models of Sepsis: Enhancement of Interleukin-10

  • Jung, Jun-Sub;Yan, Ji-Jing;Song, Dong-Keun
    • The Korean Journal of Physiology and Pharmacology
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    • v.12 no.2
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    • pp.79-81
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    • 2008
  • The effects of decursinol on various models of sepsis were investigated. Intra-peritoneal pretreatment of mice with various doses of decursinol ($1{\sim}100$ mg/kg) effectively suppressed lethality induced in three mouse models of experimental sepsis, i.e., lipopolysaccharide (LPS)/D-galactosamine (GalN), high-dose LPS (20 mg/kg), and cecal ligation and puncture (CLP). Intra-peritoneal pretreatment of mice with decursinol (50 mg/kg) markedly enhanced the LPS/GalN -induced increase of plasma interleukin-10 (IL-10) levels, without affecting plasma TNF-${\alpha}$, IL-6 and IL-12 levels. These results suggest that decursinol could be effective for prevention or treatment of sepsis.

Caspase-3-like Death Protease is Inhibited by Interleukin-7

  • Hong, Soon-Duck;Lee, Sang-Han;Tsuruo, Takashi;Lee, Dong-Sun
    • Journal of Life Science
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    • v.9 no.1
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    • pp.58-63
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    • 1999
  • Highly metastatic mouse T-lymphoma CS21 cells can grow in vitro when cocultured with CA12 lymph node stromal cells, but they undergo apoptotic cell death when separated from CA12 stromal cells. It has been found that cysteine and interleukin-7(IL-7) as antiapoptotic soluble factors that produced by CA12 stromal cells. In this study, we report that an ICE family protease is activated in CS21 cells when separated from CA12 stromal cells and cultured alone. Enzyme purification using an avidin affinity column revealed that the involved cysteine protease possessed caspase3-like death protease activity. In addition, when IL-7 was added to CS21 cell culture, the protease activity could not be detected during partial purification of the enzyme. Taken together, these results strongly suggest that the caspase3-like protease activation is suppressed by IL-7 as an antiapoptotic factor that leads to abrogation of apoptosis execution.

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Inhibitory Effect of Phorbol 12-Myristate 13-Acetate on NO Production Induced by Interleukin-1 beta in Aortic Vascular Smooth Muscle Cells of Rats (혈관평활근세포에서 Phorbol 12-Myristate 13-Acetate의 전처리가 Interleukin-1β에 의한 Nitrite생성에 미치는 영향)

  • 윤병헌;김인겸;박태규;김중영
    • Journal of Life Science
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    • v.13 no.4
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    • pp.441-447
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    • 2003
  • To examine the role of protein kinase C (PKC) in regulation of interleukin-1 beta (IL-1$\beta$)-induced iNOS expression, IL-1$\beta$-induced nitrite production was observed in cultured vascular smooth muscle (VSM) cells pretreated with phorbol 12-myristate 13-acetate (PMA) and phorbol 12,13-butyrate (PDB) as PKC activator; 4$\alpha$-phorbol-didecanoate (PDD) as PKC non-activator. Nitrite production induced by IL-1$\beta$ was increased by the presence of increasing concentration of PMA ranging from 2 to 200 nM. However, in VSM cells pretreated with PMA and PDB, IL-1$\beta$-induced $NO_2$ production was decreased in proportion to the duration of pretreatment, and most significantly decreased in pretreatment time of 24 hours. Using RT-PCR method, the expression of iNOS mRNA induced by IL-1$\beta$ was decreased in VSM cells pretreated with PMA 200 nM for 24 hours. These results suggest that decrease in IL-I$\beta$-induced nitrite production by the pretreatment of PMA result from inhibition of iNOS expression and the inhibition related to PMA-induced PKC down-regulation.