• Title/Summary/Keyword: Interleukin 12

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Cytokine Reporter Mouse System for Screening Novel IL12/23 p40-inducing Compounds

  • Im, Wooseok;Kim, Hyojeong;Yun, Daesun;Seo, Sung-Yum;Park, Se-Ho;Locksley, Richard M.;Hong, Seokmann
    • Molecules and Cells
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    • v.20 no.2
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    • pp.288-296
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    • 2005
  • Cytokines interleukin (IL) 12 and 23 play critical roles in linking innate and adaptive immune responses. They are members of heterodimeric cytokines, sharing a subunit p40. Although IL12/23 p40 is mainly induced in macrophages and dendritic cells (DCs) after stimulation with microbial Toll-like receptor ligands, methods to monitor the cells that produce IL12/23 p40 in vivo are limited. Recently, the mouse model to track p40-expressing cells with fluorescent reporter, yellow fluorescent protein, has been developed. Macrophages and DCs from these mice faithfully reported p40 induction using the fluorescent marker. Here we took advantage of these reporter mice to screen bio-compounds for p40-inducing activity. After screening hundreds of compounds, we found several extracts inducing IL12/23 p40 gene expression. Treatment of DCs with these extracts induced the expression of MHC class II and co-stimulatory molecules, which implies that these might be useful as adjuvants. Next, the in vivo target immune cells of candidate compounds were examined. The reporter system can be useful to identify cells producing IL12 or IL23 in vivo as well as in vitro. Thus, our cytokine reporter system proved to be a valuable reagent for screening for immunostimulatory molecules and identification of target cells in vivo.

Inhibitory Effect of Gallic acid on Production of Interleukins in Mouse Macrophage Stimulated by Lipopolysaccharide (Gallic acid가 Lipopolysaccharide로 활성화된 마우스 대식세포의 인터루킨 생성에 미치는 영향)

  • Park, Wan-Su
    • Journal of Pharmacopuncture
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    • v.13 no.3
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    • pp.63-71
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    • 2010
  • Objectives: Gallic acid (GA) is the major component of tannin which could be easily founded in various natural materials such as green tea, red tea, grape juice, and Corni Fructus. The purpose of this study is to investigate the effect of Gallic acid (GA) on production of interleukin (IL) in mouse macrophage Raw 264.7 cells stimulated by lipopolysaccharide (LPS). Methods: Productions of interleukins were measured by High-throughput Multiplex Bead based Assay with Bio-plex Suspension Array System based on $xMAP^{(R)}$ (multi-analyte profiling beads) technology. Firstly, cell culture supernatant was obtained after treatment with LPS and GA for 24 hour. Then, it was incubated with the antibody-conjugated beads for 30 minutes. And detection antibody was added and incubated for 30 minutes. And Strepavidin-conjugated Phycoerythrin (SAPE) was added. After incubation for 30 minutes, the level of SAPE fluorescence was analyzed on Bio-plex Suspension Array System and concentration of interleukin was determined. Results: The results of the experiment are as follows. 1. GA significantly inhibited the production of IL-3, IL-10, IL-12p40, and IL-17 in LPS-induced mouse macrophage RAW 264.7 cells at the concentration of 25, 50, 100, 200 uM (p<0.05). 2. GA significantly inhibited the production of IL-6 in LPS-induced mouse macrophage RAW 264.7 cells at the concentration of 50, 100, 200 uM (p<0.05). 3. GA diminished the production of some cytokine such as IL-4, IL-5, and IL-13 in LPS-induced mouse macrophage RAW 264.7 cells. 4. GA did not show the inhibitory effect on the production of IL-$1{\alpha}$ and IL-9 in LPS-induced mouse macrophage RAW 264.7 cells. Conclusions: These results suggest that GA has anti-inflammatory activity related with its inhibitory effects on the production of interleukins such as IL-3, IL-10, IL-12p40, IL-17, and IL-6 in LPS-induced macrophages.

Inhibition of Tumor Growth through Macrophage Activation by Polysaccharide Fraction from Peonia japonica (PJ-P) (백작약 조다당분획에 의한 대식세포 활성화를 통한 암세포 증식 억제)

  • 박혜란;정우희;정일윤;이성태;조성기
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.32 no.1
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    • pp.149-154
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    • 2003
  • The immunomodulatory activity of PJ-P, a polysaccharide fraction extracted from Paeonia japonica, were reported in our previous paper. In the present study, we investigated that PJ-P inhibited cancer growth through activation of macrophages. The activities of peritoneal macrophage to induce tumor necrosis factor (TNF)-$\alpha$, interleukin-1 (IL-1)$\beta$, interleukin-6 (IL-6) and interleukin-12 (IL-12) as well as to ingest fluorescence-latex microbeads were enhanced by treatment of PJ-P. Direct cytocidal activity of PJ-P against cancer cells was not shown. However, in vitro, peritoneal macrophages treated with PJ-P had an activity to kill cancer cells. Furthermore, PJ-P significantly prolonged the survival of mice implanted intraperitoneally with B16F0 mel-anoma cells. These results suggest that PJ-P could be a useful immunomodulator and assistant of anti-tumor agent.

The Effect of Caffeine on 3T3-L1 Adipocyte Differentiation : A Nutrigenomical Approach (Caffeine이 지방세포주 3T3-L1 분화에 미치는 영향: 영양유전체학적 접근)

  • Kim Mi-Ja;Kim Youngok;Chung Joo-HO;Kim Jong-Woo;Kim Hye-Kyung
    • Journal of Nutrition and Health
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    • v.38 no.8
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    • pp.649-655
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    • 2005
  • Nutrigenomics refers to research that investigates the interaction between nutrition and the human genome. Caffeine in tea and coffee is widely and routinely consumed by people. This study was performed to confirm the effect of caffeine treatment on the gene expression and cytokine profiling in 3T3-L1 adipocyte cells using microarray and protein array methodology. Treatment of caffeine in 3T3-L1 adipocyte cells increased expression of several genes related with obesity including adipocyte C1Q and collagen domain containing (ACDC), Adipsin (ADN), uncoupling protein 3(UCP3), while glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which is known as lipid storage enzyme, was decreased by caffeine treatment. Furthermore, cytokines, such as interleukin-3 (IL-3), interleukin-12(IL-12), interleukin-13 (IL-13), granulocyte colony stimulating factor (GCSF), granulocyte macrophage colony stimulating factor (GM-CSF) and vascular endothelial growth factor (VEGF), were decreased in caffeine treated 3T3-L1 adipocyte cells. These results provided interesting information about the genes related with caffeine and cytokine expression profiling in obesity.

Fermented red ginseng and ginsenoside Rd alleviate ovalbumin-induced allergic rhinitis in mice by suppressing IgE, interleukin-4, and interleukin-5 expression

  • Kim, Hye In;Kim, Jeon-Kyung;Kim, Jae-Young;Han, Myung Joo;Kim, Dong-Hyun
    • Journal of Ginseng Research
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    • v.43 no.4
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    • pp.635-644
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    • 2019
  • Background: To increase the pharmacological effects of red ginseng (RG, the steamed root of Panax ginseng Meyer), RG products modified by heat process or fermentation have been developed. However, the antiallergic effects of RG and modified/fermented RG have not been simultaneously examined. Therefore, we examined the allergic rhinitis (AR)-inhibitory effects of water-extracted RG (wRG), 50% ethanol-extracted RG (eRG), and bifidobacteria-fermented eRG (fRG) in vivo. Methods: RBL-2H3 cells were stimulated with phorbol 12-myristate-13-acetate/A23187. Mice with AR were prepared by treatment with ovalbumin. Allergic markers IgE, tumor necrosis factor-${\alpha}$, interleukin (IL)-4, and IL-5 were assayed in the blood, bronchoalveolar lavage fluid, nasal mucosa, and colon using enzyme-linked immunosorbent assay. Mast cells, eosinophils, and Th2 cell populations were assayed using a flow cytometer. Results: RG products potently inhibited IL-4 expression in phorbol 12-myristate-13-acetate/A23187-stimulated RBL-2H3 cells. Of tested RG products, fRG most potently inhibited IL-4 expression. RG products also alleviated ovalbumin-induced AR in mice. Of these, fRG most potently reduced nasal allergy symptoms and blood IgE levels. fRG treatment also reduced IL-4 and IL-5 levels in bronchoalveolar lavage fluid, nasal mucosa, and reduced mast cells, eosinophils, and Th2 cell populations. Furthermore, treatment with fRG reduced IL-4, IL-5, and IL-13 levels in the colon and restored ovalbumin-suppressed Bacteroidetes and Actinobacteria populations and ovalbumin-induced Firmicutes population in gut microbiota. Treatment with ginsenoside Rd significantly alleviated ovalbumin-induced AR in mice. Conclusion: fRG and ginsenoside Rd may alleviate AR by suppressing IgE, IL-4, IL-5, and IL-13 expression and restoring the composition of gut microbiota.

The Effects of Anti-cancer and Immune Response of Lonicerae Flos Herbal-acupuncture (금은화약침(金銀花藥鍼)의 항암 및 면역반응에 관한 실험적 연구)

  • Park, Hee-Soo;Han, Jae-Sub
    • Journal of Acupuncture Research
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    • v.23 no.4
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    • pp.205-218
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    • 2006
  • Objectives : This study was performed to investigate the effects of anti-cancer and changes In immune response of Lonicerge Flos Herbal-acupuncture. Methods Experimental studies were evaluated through the anti-cancer and immune response activities such as, cell viability, BNA fragmentation, Apoptosis, survival time, pulmonary colonization, and productivity of interleukins & $interferon-{\gamma}$. In order to study the effects of anti-cancer and changes in immune response of Lonicerae Flos Herbal-acupuncture, the groups were divided into five groups ; Normal group(non treated group), Control A group(0.2ml Normal saline for oral administration), Control B group(administration of intramuscular injection with 0.2ml Lonicerae Flos Herbal-acupuncture solution), Acupuncture group(AT, administration of acupuncture at Chungbu(L1)), and Herbal-Acupuncture group(HAT, administration of Lonicerae Flos Herbal-acupuncture at Chungbu(L1)). Results : 1. Lonicerae Flos Herbal-acupuncture(>300mg/ml) could lead cancer cell to cell death. 2. Lonicerae Flos Herbal - acupuncture (40mg/ml) caused DNA cleavage. 3. Lonicerae Flos Herbal-acupuncture(400mg/ml) caused apoptosis in the cancer cell line. 4. In mouse survival time, all of experimental groups didn't show any significant compared to the control group. 5. In pulmonary colonization assay, Lonicerae Flos Herbal-acupuncture group was less than Control A group at 7 days after induction of cancer. 6. In comparison Control A group, there was significant decrease of Interleukin-2 level in Lonicerae Flos Herbal-acupuncture group. 7. In comparison Control group, there was decrease of Interleukin-4 level in the Acupuncture group. 8. In comparison Control group, there was decrease of Interleukin-10 level in the Acupuncture group. 9. In comparison Control group, there was significant increase of Interleukin-12 level in Acupuncture group and Lonicerae Flos Herbal-acupuncture group. 10. In comparison Control group, there was significant increase of $Interferon-{\gamma}$ level in Acupuncture group. Conclusion : According to above mentioned results, Lonicerae Flos Herbal- acupuncture is expected to be effective for anticancer and improvement in immune response.

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Genetic Polymorphism of Interleukin-1A (IL-1A), IL-1B, and IL-1 Receptor Antagonist (IL-1RN) and Prostate Cancer Risk

  • Xu, Hua;Ding, Qiang;Jiang, Hao-Wen
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.20
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    • pp.8741-8747
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    • 2014
  • Purpose: We aimed to investigate the associations between polymorphisms of interleukin-1A (IL-1A), IL-1B, and IL-1 receptor antagonist (IL-1RN) and prostate cancer (PCa) risk. Materials and Methods: A comprehensive search for articles of MEDLINE and EMBASE databases and bibliographies of retrieved articles published up to August 3, 2014 was performed. Methodological quality assessment of the trials was based on a standard quality scoring system. The meta-analysis was performed using STATA 12.0. Results: We included 9 studies (1 study for IL-1A, 5 studies for IL-1B, and 3 studies for IL-1RN), and significant association was found between polymorphisms of IL-1B-511 (rs16944) as well as IL-1B-31 (rs1143627) and PCa risk. IL-1B-511 (rs16944) polymorphism was significantly associated with PCa risk in homozygote and recessive models, as well as allele contrast (TT vs CC: OR, 0.74; 95%CI, 0.58-0.94; P=0.012; TT vs TC+CC; OR, 0.79; 95%CI, 0.63-0.98; P=0.033; T vs C: OR, 0.86; 95%CI, 0.77-0.96; P=0.008). The association between IL-1B-31 (rs1143627) polymorphism and PCa risk was weakly significant under a heterozygote model (OR, 1.35; 95%CI, 1.00-1.80; P=0.047). Conclusions: Sequence variants in IL-1B-511 (rs16944) and IL-1B-31 (rs1143627) are significantly associated with PCa risk, which provides additional novel evidence that proinflammatory cytokines and inflammation play an important role in the etiology of PCa.

Effects of 12 Weeks Tai Chi Exercise and Education Intervention Program on Glucose Control, Sexual Function and Immune Function for Women with Type 2 Diabetes (타이치 운동과 교육 중재 프로그램이 제 2형 여성당뇨환자의 당대사, 성기능 장애 및 면역기능에 미치는 효과)

  • Park, Hyoung Sook;Kim, Kyoungnam
    • Journal of Korean Academy of Fundamentals of Nursing
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    • v.20 no.4
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    • pp.389-399
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    • 2013
  • Purpose: This study was done to identify effects of a 12 weeks Tai Chi exercise and education intervention program on HbA1C, sexual function and IL-12 (Interleukin 12), IL-4 (Interleukin 4), TNF-${\alpha}$ (Tumor Necrosis Factor) for women with type 2 diabetes. Methods: The study had a nonequivalent control group pretest posttest design. The participants were 64 women with diabetes recruited from an outpatient clinic of a university hospital. The Tai Chi exercise and education intervention program was provided twice a week for 12 weeks for the 32 women in the experimental group. The 32 women in the control group were maintained on basic outpatient treatment. Outcome variables were HbA1C, sexual dysfunction scores, IL-4, IL-12 and TNF-${\alpha}$. Results: The experimental group showed significantly improved HbA1C (F=3.10, p=.004), and sexual function (F=3.78, p=.001) compared to the control group. Also for the experimental group TNF-${\alpha}$ (F=-2.69, p=.004) significantly increased compared to the control group. Conclusion: Results indicate that a Tai Chi exercise and education intervention program can be utilized effectively for women with type 2 diabetes.

Study on Alteration of Interleukin-$1{\beta}$, -2, -6 Production and Serum Level in Schizophrenic Patients (정신분열증 환자에서 Interleukin-$1{\beta}$, -2, -6 생산능과 혈청농도 변화에 관한 연구)

  • Kim, Yong-Ku;Lee, Min-Soo;Suh, Kwang-Yoon
    • Korean Journal of Biological Psychiatry
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    • v.1 no.1
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    • pp.98-108
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    • 1994
  • The etiology and pathophysiology of schizophrenia remain unknown. It has been postulated that infectious-autoimmune process may play a role in the pathogenesis of symptoms in some schizophrenic patients. Findings of altered interleukin(IL) regulation have been regarded as additional proof that schzophrenia has an infectious-autoimmune background. In the present study, we measured mitogen-stimulated production of and serum level of IL-$1{\beta}$, IL-2, IL-6 using ELISA in 16 neuroleptic-free schizophrenic patients and in 16 age, sex matched healthy controls. The results were as follows : 1) There was a significant decrease of IL-2 production in schizophrenic patients than in normal controls(respectively $1.90{\pm}0.13ng/m{\ell}$, $2.79{\pm}0.14ng/m{\ell}$, p<0.001). But there was no significant difference of IL-$1{\beta}$ production and IL-6 production between schizophrenic patients and normal controls. 2) There was a significant increase of serum level of IL-2 in schizophrenic pateitns than in normal controls(respectively $184.8{\pm}12.8pg/m{\ell}$, $104.2{\pm}34.2pg/m{\ell}$, p<0.01). Serum level of IL-$1{\beta}$ was partially detected in both groups and serum level of IL-6 was not detected in both groups. 3) There was no significant differences of IL-$1{\beta}$, -2, -6 production & serum level of IL-2 according to male vs female, paranoid type vs undifferentiated type, drug-naive group vs drug-free group in schizophrenic patients. 4) There was significant correlation between IL-$1{\beta}$ and IL-6 production(r=0.86, p<0.001). No correlation between IL-$1{\beta}$, -2, -6 production, serum level of IL-2 and age, duration of illness, and BPRS score was found. It has been suggested that the low lymphocyte production of IL-2 in the patients with autoimmune disease occurs because the T cells are activated and lymphocyte-derived IL-2 has been released into the serum. The authors suggest that decreased IL-2 production in our schizophrenic patients is due to increased IL-2 serum level in those patients. Thus our finding of low IL-2 production and high serum level of IL-2 in our schizophrenic patients is compatible with the possibility that our patients have an autoimmune process. Further study on relationship between IL alteration and other immunological abnormalities(the presence of serum autoantibody and of anti-brain antibody, $CD4^+$, $CD8^+$ cell index, etc) in schizophrenic patients will be warranted.

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Microarray Analysis of Gene Expression in Chondrosarcoma Cells Stimulated with Bee Venom (봉독이 연골육종세포의 유전자 발현에 미치는 영향에 대한 Microarray 연구)

  • Yin, Chang-Shik;Koh, Hyung-Gyun
    • Journal of Pharmacopuncture
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    • v.7 no.2
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    • pp.19-28
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    • 2004
  • 봉독은 관절염 치료를 비롯한 여러 질환에 그 응용범위가 넓어지고 있으며 기전규명과 새로운 치료효과 개발을 위한 연구가 필요하다. 연골의 파괴는 진행된 각종 관절병증의 공통 병리기전이며 연골세포의 기능이상은 이 기전에 중요한 의미를 지닌다. 사람 연골세포의 특성을 유지하고 있는 HTB-94 연골육종세포를 배양하고 봉독을 처치했을 때의 유전자 발현양상을 microarray를 이용하여 관찰하였다. 대조군에 비해 4배 이상 발현의 차이가 있는 경우를 유의한 것으로 보았을 때 microarray의 344개 유전자중 봉독처치시 발현이 증강되는 유전자는 없었으며 발현이 억제되는 유전자는 interleukin 6 receptor, interleukin 1 alpha, tissue inhibitor of metalloproteinase 1, matrix metalloproteinase 1, tumor necrosis factor (ligand) superfamily, members 4, 8 and 12, and caspases 2, 6, and 10등 35개가 관찰되었다. Microarray를 통한 유전자발현 분석을 통해 관절염에 대한 봉독치료의 기전을 시사하는 유용한 자료를 얻을 수 있었으며 앞으로 보다 넓은 범위에 대한 연구가 필요할 것이다.