• Title, Summary, Keyword: cytokine

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PEP-1-paraoxonase 1 fusion protein prevents cytokine-induced cell destruction and impaired insulin secretion in rat insulinoma cells

  • Lee, Su Jin;Kang, Hyung Kyung;Choi, Yeon Joo;Eum, Won Sik;Park, Jinseu;Choi, Soo Young;Kwon, Hyeok Yil
    • BMB Reports
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    • v.51 no.10
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    • pp.538-543
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    • 2018
  • Pancreatic beta cell destruction and dysfunction induced by cytokines is a major cause of type 1 diabetes. Paraoxonase 1 (PON1), an arylesterase with antioxidant activity, has been shown to play an important role in preventing the development of diabetes in transgenic mice. However, no studies have examined the anti-diabetic effect of PON1 delivered to beta cells using protein transduction. In this study, we expressed the cell-permeable PON1 fused with PEP-1 protein transduction domain (PEP-1-PON1) to investigate whether transduced PEP-1-PON1 protects beta cells against cytokine-induced cytotoxicity. PEP-1-PON1 was effectively delivered to INS-1 cells and prevented cytokine-induced cell destruction in a dose-dependent manner. Transduced PEP-1-PON1 significantly reduced the levels of reactive oxygen species (ROS) and nitric oxide (NO), DNA fragmentation, and expression of inflammatory mediators, endoplasmic reticulum (ER) stress proteins, and apoptosis-related proteins in cytokine-treated cells. Moreover, transduced PEP-1-PON1 restored the decrease in basal and glucose-stimulated insulin secretion induced by cytokines. These data indicate that PEP-1-PON1 protects beta cells from cytokine-induced cytotoxicity by alleviating oxidative/nitrosative stress, ER stress, and inflammation. Thus, PEP-1-mediated PON1 transduction might be an effective method to reduce the extent of destruction and dysfunction of pancreatic beta cells in autoimmune diabetes.

Evaluation of the Immune Response Following Exposure of Mice to Bisphenol A: Induction of Th1 Cytokine and Prolactin by BPA Exposure in the Mouse Spleen Cells

  • Youn, Ji-Youn;Park, Hyo-Young;Lee, Jung-Won;Jung, In-Ok;Choi, Keum-Hwa;Kim, Kyung-Jae;Cho, Kyung-Hea
    • Archives of Pharmacal Research
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    • v.25 no.6
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    • pp.946-953
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    • 2002
  • Bisphenol A [2, 2 bis (4-hydoxyphenyl) propane; BPA] is a widely used endocrine disruptors and has estrogenic: activities. Although interests on biological effect of BPA are rising, evidences of its effect on immune system are lacking. We investigated that the effect of BPA on immune parameters to postulate the mechanism, and BPA interruptions between neuroendocrine and immune system. BPA was administrated to mice by p.o. (as a drinking water) dose on 0.015, 1.5 and 30 mg/ml for 4 weeks. The BPA treatment did not result in any change in body weight, spleen weight and distribution of lymphocyte subpopulation collected from spleen. BPA induced prolactin production in spleen, and exposure of SPA increased the activity of splenocyte proliferation in response to Con A (p<0.001). The production of a strong Th-1 type cytokine ($IFN-{\gamma}$) was induced while Th-2 type (IL-4) was suppressed by SPA treatment. These were consistent with RT-PCR results of transcription factor GATA-3 and IRF-1. These findings suggested that stimulation of prolactin production by estrogenic effects of SPA would affect cytokine profiles, and lead to imbalanced cellular immune response. In addition, we could speculate that prolactin and cytokine is important mediator involved in network between neuroendocrine and immune system by BPA.

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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In Vitro Effects of Water and Methanol Extracts of Melittia inouei on Cytokine Production (유리나방 유충 추출물이 비장 세포로부터 Cytokine 분비에 미치는 효과)

  • Lee, Hyun-Ah;Shon, Hye-Jin;Yang, Young-Taek;Kim, Kyu-Don;Park, Hae-Cheol;Hwang, Jae-Sam;Hwang, Suk-Jo;Ahn, Mi-Young
    • Korean Journal of Pharmacognosy
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    • v.37 no.2
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    • pp.110-115
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    • 2006
  • Melittia inouei (Yuri Nabang) larvae are used as a crude drug in East Asia for treating stomach cancer and inflammation, and currently reared as a pharmaceutical insect in Jejudo, Korea. This study evaluated the immuno-modulating activity of these extracts, by determining the level of, cytokine production from mouse splenocytes stimulated with the extracts. The Melittia inouei larvae extracts did not induce the splenocyte proliferation. On the other hand, they stimulated the splenocytes to produce cytokines such as $TNF-{\alpha}$, whereas they did not stimulate IL10, IL12 or $IFN-{\gamma}$. The aqueous portion of its plant (Tri-chosanthis kirilowii) extract (sap) was found to be a potent inducer of NO production from the CPAE cells. However, it showed weak inhibitory effects on vascular endothelial growth factor (VEGF) production from splenocytes. These data suggests that a Melittia inouei larvae extract immune modulatory activity in cytokine prodcutions such as $TNF-{\alpha}$ and VEGF which might be related its anticancer effect.

Enhancing Effect of Sorghum bicolor L. Moench (Sorghum, su-su) Extracts on Mouse Spleen and Macrophage Cell Activation (수수 추출물에 의한 마우스 비장세포 및 대식세포 활성의 항진 효과)

  • Ryu Hye-Sook;Kim Jin;Kim Hyun-Sook
    • The Korean Journal of Food And Nutrition
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    • v.19 no.2
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    • pp.176-182
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    • 2006
  • Sorghum bicolor L. Moench(Sorghum, Su-Su) is a major cereal food crop used in many parts of the world. It is used as a human food resource and folk medicines in Asia and Africa. The stem of sorghum has been used as a digestive aid and an anti-diarrheal agent. Sorghum hybrids contain high levels of diverse phenolic compounds that may provide health benefits. High levels of polyflavanols, anthocyanins, phenolic acids, and other antioxidant compounds have been reported in sorghums, which have also been shown to possess various biological activities such as anti-mutagenic, anti-carcinogenic, and HMG-CoA reductase inhibitory activities. In an in vitro experiment, we examined mice splenocyte proliferation and production of three types of cytokine($IL-1{\beta},\;IL-6,\;TNF-{\alpha}$) by peritoneal macrophages cultured with ethanol and water extracts of Sorghum bicolor L. Moench. A single cell suspension of splenocytes was prepared and the cell proliferation of the splenocytes was examined by MTT assay. The splenocyte proliferation was increased when water extracts of Sorghum bicolor L. Moench were used as supplements in all concentrations investigated. The production of cytokine($IL-1{\beta},\;IL-6,\;TNF-{\alpha}$) by activated peritoneal macrophage was detected by ELISA using the cytokine kit. $IL-1{\beta},\;IL-6,\;and\;TNF-{\alpha}$ production by activated macrophages were increased by supplementation with Sorghum bicolor L. Moench water extracts. This study suggests that supplementation of with Sorghum bicolor L. Moench water extracts may enhance immune function by regulating the splenocyte proliferation and enhancing the cytokine production by activated macrophages in vitro.

Effects of Patrinia Scabiosaefolia Aqueous Extract on Cytokine and NF-κB Activation in LPS-induced RAW 264.7 Cells and Mouse (패장(敗醬) 물 추출물의 LPS로 유도된 RAW 264.7 세포와 mouse 염증모델에서 cytokine 및 NF-κB의 활성에 미치는 효과)

  • Ryu, Ik-Han;Cho, Hae-Joong;Song, Mi-Hwa;Choi, Chang-Min
    • The Journal of Korean Obstetrics and Gynecology
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    • v.30 no.2
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    • pp.1-15
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    • 2017
  • Objectives: The object of this study was to identify the anti-inflammatory effects of Patrinia scabiosaefolia aqueous extract (PSE). Methods: RAW 264.7 cells were pre-treated with PSE and then incubated with or without lipopolysaccharide (LPS). Cell viability, production of nitric oxide (NO), secretion of pro-inflammatory cytokine, activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-${\kappa}B$) were measured. In addition, we observed mice survival rate after LPS and their cytokine levels of serum. We also observed inflammatory and hemorrhagic change on the histological sections of the liver. Results: PSE inhibited LPS-induced NO production, interleukin (IL)-6 secretion, c-Jun NH2-terminal kinase (JNK) and NF-${\kappa}B$ activation. In addition, PSE reduced the death rate of LPS-induced mice and IL-6 production on the serum of mice. PSE inhibited inflammation and hemorrhage on liver tissue as well. Conclusions: The results suggest that PSE have anti-inflammatory effects by inhibited NF-${\kappa}B$ and JNK activation, IL-6 secretion, and NO production. So PSE may be effective treatment for the inflammatory disease.

Naegleria fowleri Lysate Induces Strong Cytopathic Effects and Pro-inflammatory Cytokine Release in Rat Microglial Cells

  • Lee, Yang-Jin;Park, Chang-Eun;Kim, Jong-Hyun;Sohn, Hae-Jin;Lee, Jin-Young;Jung, Suk-Yul;Shin, Ho-Joon
    • The Korean Journal of Parasitology
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    • v.49 no.3
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    • pp.285-290
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    • 2011
  • Naegleria fowleri, a ubiquitous free-living ameba, causes fatal primary amebic meningoencephalitis in humans. N. fowleri trophozoites are known to induce cytopathic changes upon contact with microglial cells, including necrotic and apoptotic cell death and pro-inflammatory cytokine release. In this study, we treated rat microglial cells with amebic lysate to probe contact-independent mechanisms for cytotoxicity, determining through a combination of light microscopy and scanning and transmission electron microscopy whether N. fowleri lysate could effect on both necrosis and apoptosis on microglia in a time- as well as dose-dependent fashion. A $^{51}Cr$ release assay demonstrated pronounced lysate induction of cytotoxicity (71.5%) toward microglial cells by 24 hr after its addition to cultures. In an assay of pro-inflammatory cytokine release, microglial cells treated with N. fowleri lysate produced TNF-${\alpha}$, IL-6, and IL-$1{\beta}$, though generation of the former 2 cytokines was reduced with time, and that of the last increased throughout the experimental period. In summary, N. fowleri lysate exerted strong cytopathic effects on microglial cells, and elicited pro-inflammatory cytokine release as a primary immune response.

Immunomodulatory effects of chlorogenic acid and ethyl acetate fraction from Lonicera japonica on cytokine gene expression profiles in spleen and thymus (Chlorogenic acid 및 인동등 ethyl acetate 분획의 비장 및 흉선 세포에서의 유전자 발현 분석을 통한 면역조절효과)

  • Ha, Tae-Kwang;Lee, Young-Cheol
    • The Korea Journal of Herbology
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    • v.26 no.2
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    • pp.1-10
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    • 2011
  • Objective : Lonicera japonica contains anti complementary polysaccharides and polyphenolic compound. Among these polyphenolic substances, chlorogenic acid is the major active component of this plant. However, the immunological mechanisms for these activities, have not been elucidated, nor the active components. To clarify immunomodulatory effects of those we examined the relationship between the activity of CD8+ T cell-mediated lysis and the frequency of cytokine profiles in spleen, thymus (especially IFN-${\gamma}$, IL-4, GM-CSF etc.) expressing CD8+ T cells activated by IL-2. Methods : To study immunomodulatory effects ethyl acetate fraction from Lonicera japonica, chlorogenic acid on cytokine gene expression from spleen, thymus cells, RT-PCR was performed after quantitative normalization for each gene by a densitometry using ${\beta}$-actin gene expression. A modified standard $^{51}Cr$-release assay was used to measure cytotoxic activities of cytotoxic T cells. Spleen, thymus cells from NOD mice were stained with CD3, CD4, CD44, CD69 in staining buffer and analyzed by two color flow cytometry. Results : We showed that ethyl acetate fraction from Lonicera japonica in combination with IL-2 resulted in a significant enhancement of PCR products for IFN-${\gamma}$, IL-4, IL-10, GM-CSF, IL-6 and cytotoxtic CD8+ T cell proportion in spleen and thymus T cells in NOD mice. This suggests that IFN-${\gamma}$, IL-6 like IL-4 may be acting as a regulatory rather than proinflammatory cytokine. Conclusions : In conclusion, based on the results of the present study which showed that ethyl acetate fraction from Lonicera japonica and chlorogenic acid upregulating cytokine gene expression in spleen and thymus, we are tempted to speculate that some of the therapeutic efficacies such as anti-diabetic activity of Lonicera japonica are due to the immunomodulatory its ethylacetate fraction and chlorogenic acid.

Effects of resistance training on the inflammatory response

  • Celle, Mariana C.;Fernandez, Maria Luz
    • Nutrition Research and Practice
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    • v.4 no.4
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    • pp.259-269
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    • 2010
  • Resistance training (RT) is associated with reduced risk of low grade inflammation related diseases, such as cardiovascular disease and type 2 diabetes. The majority of the data studying cytokines and exercise comes from endurance exercise. In contrast, evidence establishing a relationship between RT and inflammation is more limited. This review focuses on the cytokine responses both following an acute bout, and after chronic RT. In addition, the effect of RT on low grade systemic inflammation such as individuals at risk for type 2 diabetes is reviewed. Cytokines are secreted proteins that influence the survival, proliferation, and differentiation of immune cells and other organ systems. Cytokines function as intracellular signals and almost all cells in the body either secrete them or have cytokine receptors. Thus, understanding cytokine role in a specific physiological situation such as a bout of RT can be exceedingly complex. The overall effect of long term RT appears to ameliorate inflammation, but the specific effects on the inflammatory cytokine, tumor necrosis factor alpha are not clear, requiring further research. Furthermore, it is critical to differentiate between chronically and acute Interleukin-6 levels and its sources. The intensity of the RT and the characteristics of the training protocol may exert singular cytokine responses and as a result different adaptations to exercise. More research is needed in the area of RT in healthy populations, specifically sorting out gender and age RT acute responses. More importantly, studies are needed in obese individuals who are at high risk of developing low grade systemic inflammatory related diseases. Assuring adherence to the RT program is essential to get the benefits after overcoming the first acute RT responses. Hence RT could be an effective way to prevent, and delay low grade systemic inflammatory related diseases.

Effects of CpG Oligodeoxynucleotides on Immune Responses and Expression of Cytokine Genes in Cultured Olive Flounder Paralichthys olivaceus

  • Ahn, kyoung-Jin;Nam, Bo-Hye;Kim, Young-Ok;Kang, Jung-Ha;Kim, Bong-Seok;Jee, Young-Ju;Lee, Sang-Jun
    • Fisheries and aquatic sciences
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    • v.10 no.1
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    • pp.1-7
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    • 2007
  • The induction of cellular and humoral immunity and cytokine gene expression by synthetic CpG oligodexoynucleotides (CpG-ODNs) has not been investigated systematically in olive flounder Paralichthys olivaceus in vivo. We optimized the proper concentration of CpG-ODNs using an in vitro assay for the superoxide anion $(O_2^-)$. CpG-ODNs induced $O_2^-$ and nitric oxide (NO) production, lysozyme activity, and the proinflammatory cytokine gene expression of $IL-1{\beta}$ and $TNF-{\alpha}$ in olive flounder significantly in vivo, whereas non-CpG-ODNs did not produce these effects or produced them to a lesser extent. This implied that CpG-ODNs could stimulate cellular and humoral immunity and cytokine gene expression in olive flounder. This is the first evidence of NO production and the first study on the mRNA expression of the proinflammatory cytokine genes $IL-1{\beta}$ and $TNF-{\alpha}$ in olive flounder in response to CpG-ODNs. Comparison of the variation in NO production and lysozyme activity to that of other studies led us to postulate that a group-specific difference exists in the immune responses of olive flounder against CpG-ODNs. Furthermore, the detailed immunostimulatory spectrum of CpG-ODNs in olive flounder could be a useful index with which to analyze the effect of CpG-ODNs against the challenge test prior to field applications.