• Title/Summary/Keyword: Interleukin-17

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Antiinflammatory and Myocardial Protective Effects of Magnesium in Patents Undergoing Valvular Heart Surgery (심장판막 수술 시 마그네슘의 항염증 및 심근보호 효과)

  • Moon, Seong-Min;Kang, Shin-Beum;Hyun, Kyung-Yae;Choi, Seok-Cheol
    • Journal of Life Science
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    • v.17 no.11
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    • pp.1539-1546
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    • 2007
  • We have investigated whether the supplement of magnesium to cold blood cardioplegia improves myocardial protection. Sixty patients scheduled for elective valvular heart surgery were randomly assigned to a control group (n=30) which received conventional cold blood cardioplegia and an Mg group (n=30) which received cold blood cardioplegia supplemented with 2 g of magnesium sulfate. Electrolytes levels including $Mg^{++}$, hematological and biochemical variables, cytokines, myocardial marker levels, and postoperative outcomes were compared between two groups before, during or idler operation. $Mg^{++}\;and\;Ca^{++}$ levels in the Mg group were higher than those of the control group after surgery. The total WBC counts, CK-MB, troponin-I and Interleukin-6 levels in the Mg group were lower than those of the control group after surgery. Postoperative incidence of atrial fibrillation was lower in the Mg group compared with the control group. These results showed that $Mg^{++}$ attenuated inflammatory reaction, myocardial damage, and hypomagnesemia during valvular surgery and reduced postoperative arrhythmia incidence without side effects.

Interleukin-2/antibody complex expanding Foxp3+ regulatory T cells exacerbates Th2-mediated allergic airway inflammation

  • Hong, Sung-Wook;O, Eunju;Lee, Jun Young;Yi, Jaeu;Cho, Kyungjin;Kim, Juhee;Kim, Daeun;Surh, Charles D.;Kim, Kwang Soon
    • BMB Reports
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    • v.52 no.4
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    • pp.283-288
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    • 2019
  • $Foxp3^+$ regulatory $CD4^+$ T (Treg) cells play an essential role in preventing overt immune responses against self and innocuous foreign antigens. Selective expansion of endogenous Treg cells in response to the administration of interleukin (IL)-2/antibody complex, such as the IL-2/JES6-1 complex (IL-2C) in mice, is considered an attractive therapeutic approach to various immune disorders. Here, we investigated the therapeutic potential of IL-2C in allergic airway inflammation models. IL-2C treatment ameliorated Th17-mediated airway inflammation; however, unexpectedly, IL-2C treatment exacerbated Th2-mediated allergic airway inflammation by inducing the selective expansion of Th2 cells and type-2 innate lymphoid cells. We also found that IL-2 signaling is required for the expansion of Th2 cells in lymphoproliferative disease caused by Treg cell depletion. Our data suggest that IL-2C is selectively applicable to the treatment of allergic airway diseases depending on the characteristics of airway inflammation.

Fatty Acid Binding Protein 5 (FABP5) Promotes Aggressiveness of Gastric Cancer Through Modulation of Tumor Immunity

  • Mei-qing Qiu;Hui-jun Wang;Ya-fei Ju;Li Sun;Zhen Liu;Tao Wang;Shi-feng Kan;Zhen Yang;Ya-yun Cui;You-qiang Ke;Hong-min He;Shu Zhang
    • Journal of Gastric Cancer
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    • v.23 no.2
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    • pp.340-354
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    • 2023
  • Purpose: Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC. Materials and Methods: We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq). Results: Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokine-cytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics. Conclusions: These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.

Ginsenoside F2 attenuates chronic-binge ethanol-induced liver injury by increasing regulatory T cells and decreasing Th17 cells

  • Kim, Myung-Ho;Kim, Hee-Hoon;Jeong, Jong-Min;Shim, Young-Ri;Lee, Jun-Hee;Kim, Ye Eun;Ryu, Tom;Yang, Keungmo;Kim, Kyu-Rae;Jeon, Byeong-Min;Kim, Sun Chang;Jung, Jae-Kwang;Choi, Jae-Kap;Lee, Young-Sun;Byun, Jin-Seok;Jeong, Won-Il
    • Journal of Ginseng Research
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    • v.44 no.6
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    • pp.815-822
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    • 2020
  • Background: Recently, beneficial roles of ginsenoside F2 (GF2), a minor constituent of Panax ginseng, have been demonstrated in diverse inflammatory diseases. However, its roles in alcoholic liver inflammation and injury have not been clearly understood. Here, we investigated the underlying mechanism by which GF2 ameliorated alcoholic liver injury. Methods: To induce alcoholic liver injury, C57BL/6J wild type (WT) or interleukin (IL)-10 knockout (KO) mice were orally administered with ethanol (3 g/kg) or ethanol-containing GF2 (50 mg/kg) for 2 wk. Liver injury and infiltration of macrophages and neutrophils were evaluated by serum biochemistry and immunohistochemistry, respectively. The changes of hepatic immune cells were assessed by flow cytometry and polymerase chain reaction analysis. In vitro differentiation of naïve T cells was performed. Results: GF2 treatment significantly attenuated alcoholic liver injury, in which infiltrations of inflammatory macrophages and neutrophils were decreased. Moreover, the frequencies of Foxp3+ regulatory T cells (Tregs) increased but IL-17-producing T (Th17) cells decreased in GF2-treated mice compared to controls. Furthermore, the mRNA expression of IL-10 and Foxp3 was significantly increased, whereas IL-17 mRNA expression was suppressed in GF2-treated mice. However, these beneficial roles of GF2 were not observed in GF2-treated IL-10 KO mice, suggesting a critical role of IL-10. Similarly, GF2 treatment suppressed differentiation of naïve T cells into Th17 cells by inhibiting RORgt expression and stimulating Foxp3 expression. Conclusion: The present study suggests that GF2 treatment attenuates alcoholic liver injury by increasing IL-10 expression and Tregs and decreasing IL-17 expression and Th17 cells.

Role of Citrullinated Fibrinogen Peptides in the Activation of CD4 T Cells from Patients with Rheumatoid Arthritis

  • Shin, Kihyuk;Hong, SeokChan;Choi, Eun-Hye;Lim, Mi-Kyoung;Shim, Seung-Cheol;Ju, Ji-Hyeon;Lee, Seung-Hyo
    • IMMUNE NETWORK
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    • v.13 no.4
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    • pp.116-122
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    • 2013
  • This study was conducted to determine whether CD4 T cell responses to citrullinated fibrinogen occur in patients with rheumatoid arthritis (RA), especially in HLA-DR4-positive subjects. Whole peripheral blood mononuclear cells (PBMCs) of RA patients and control subjects were stimulated with citrullinated fibrinogen peptides, and T-cell production of proliferation and proinflammatory cytokines, such as interferon-${\gamma}$(IFN-${\gamma}$) and interleukin-17A (IL-17A), were measured. In addition, CD4 T cells from RA patients were stimulated with the citrullinated fibrinogen peptide, $Fib-{\alpha}$ R84Cit, identified as a DRB1*0401-restricted T cell epitope in HLA-DR4 transgenic mice, and the degree of T cell activation was examined similarly. No proliferative responses to the citrullinated fibrinogen peptides were observed in whole PBMCs or CD4 T cells from RA patients. Furthermore, no increased production of IFN-${\gamma}$ or IL-17A was found in whole PBMCs or CD4 T cells stimulated with the citrullinated fibrinogen peptides, although these cells responded to recall antigen, a mixture of tetanus toxoid, purified protein derivative (PPD) from Mycobacterium tuberculosis, and Candida albicans. The results of this study indicate that anti-citrulline immunity in RA patients may be mediated by fibrinogen because there is no evidence of CD4 T cell-mediated immune responses to citrullinated fibrinogen peptides.

A Clinical Study on Juheli (Recombinant Human Interleukin - 11) in the Second Prevention of Chemotherapy Induced Thrombocytopenia

  • Xiao, Yang;Liu, Jun;Huang, Xin-En;Guo, Jian-Xiong;Fu, Peng-Chao;Huang, Xiao-Hong;Zhou, Juan;Ye, Ai-Qin
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.2
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    • pp.485-489
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    • 2016
  • Objective: to investigate the effect and side effects of recombinant human interleukin - 11 (rhIL - 11, in Chinese Juheli, produced by Qi Lu Biotechnology CO., LTD) in the second prevention of chemotherapy induced thrombocytopenia (CIT). Methods: Cancer patients with CIT were recruited and were treated with rhIL - 11 (treatment phase, TP), and in the following cycle, all these patients administered with rhIL - 11 24 hours immediately after chemotherapy (preventive treatment phase, PTP). Duration and severity of thrombocytopenia between two phases were compared. Results: for patients in TP or PTP, nadir values of platelet were ($29.28{\pm}20.08){\times}10^9/L$ and ($45.24{\pm}19.66){\times}10^9/L$, duration of thrombocytopenia in TP and PTP was ($11.52{\pm}4.33$) and ($8.20{\pm}+2.77$)days, recovery time was ($19.40{\pm}3.89$)and ($13.44{\pm}3.02$)days, duration of rhIL - 11 administration was ($10.68{\pm}2.46$)and ($6.28{\pm}1.77$)days, number of patients needing platelet infusion was 16and4 respectively, all differences were statistically significant (p value were 0.007, 0.002, 0.000, 0.000, 0.034 respectively). For TP and PTP, number of patients with hemorrhage was 8 and 4, duration of bleeding was ($5.00{\pm}0.82$) and ($4.50{\pm}0.71$) days respectively, with no statistically significant difference. Adverse reactions mainly included fever, edema, arrhythmia, joint pain, fatigue, skin rash, headache, dizziness, etc., all were not statistically significant between TP and PTP. Conclusion: rhIL - 11 could be well tolerated and is effective that could reduce the duration, severity of CIT, platelet transfusion, and incidence of bleeding, as well as shorten the recovery time, duration of rhIL - 11 administration. Thus, rhIL - 11 could be commended in the second prevention of CIT for patients with cancer.

Clinical Significance of Serum Endothelin-1 and Interleukin-8 in Sepsis (패혈증에서 혈중 Endothelin-1 및 Interleukin-8의 임상적 의의)

  • Park, Kwang-Joo;Choi, Young-In;Oh, Yoon-Jung;Choi, Young-Hwa;Hwang, Sung-Chul;Lee, Yi-Hyeong
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.3
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    • pp.300-309
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    • 2001
  • Background : Sepsis is a clinical syndrome characterized by a systemic inflammatory and hemodynamic response to severe bacterial infections that involve various mediators. Endothelin (ET)-1, a potent vasoconstrictor is associated with mu1tiple organ failure, and interleukin (IL)-8, a proinflammtory cytokine, plays a major role in neurophil activation. Both have been reported to be useful parameters in the clinical assessment of sepsis. The levels of ET-1 and IL-8 in the blood were measured in patients with sepsis, and the correlation of both parameters and their relationship with the clinical data was assessed. Methods : 19 sepsis patients and 17 controls were studied. Blood samples of the sepsis patients were drawn in day 1, 3, 7, and 14. The APACHE III scores were calculated in concurrent days. The ET-1 and IL-8 levels were measured using immunoassay methods. Results : The ET-1 levels of patients with sepsis were significantly higher than in the controls. In patients with sepsis, non-survivors had higher ET-1 levels than survivors on day 1 and 7, and patients with shock also had higher ET-1 levels than normotensive patients on admission. The ET-1 levels were significantly correlated with the creatinine levels on day 1, 7, and 14. The IL-8 levels showed a significant correlation with the ET-1 levels on day 14. Conclusion : ET-1 was found to be closely related with the clinical outcome, shock, and renal failure, and showed a correlation with IL-8. These mediators can be considered not only to play pathophysiologic roles but also as useful parameters in the clinical assessment of sepsis.

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Inverse behavior of IL-23R and IL-17RA in chronic and aggressive periodontitis

  • Ruiz-Gutierrez, Alondra del Carmen;Rodriguez-Montano, Ruth;Pita-Lopez, Maria Luisa;Zamora-Perez, Ana Lourdes;Guerrero-Velazquez, Celia
    • Journal of Periodontal and Implant Science
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    • v.51 no.4
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    • pp.254-263
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    • 2021
  • Purpose: Periodontitis is associated with a dysbiosis of periodontopathic bacteria, which stimulate the interleukin (IL)-23/IL-17 axis that plays an essential role in the immunopathogenesis of this disease, leading to alveolar bone destruction through receptor activator of nuclear factor κB ligand (RANKL). IL-23 receptor mRNA (IL-23R) has been identified in periodontitis, and IL-17 receptor A mRNA (IL-17RA) and its protein have not yet been evaluated in patients with periodontitis. In this study was measure IL-23R and IL-17RA in gingival tissue (GT) from patients with generalized chronic periodontitis (GCP) and generalized aggressive periodontitis (GAP) and to explore correlations with clinical parameters. Methods: We included 16 healthy subjects (HS), 18 patients with GCP, and 14 with GAP. GT samples were collected during periodontal surgery. Both IL-23R and IL-17RA were detected by enzyme-linked immunosorbent assay. Results: The results were analyzed with Mann-Whitney U test and Spearman' rank correlation coefficients using SPSS version 25.0. We found lower IL-23R levels in patients with GCP and GAP than in HS. Contrarily, we observed higher IL-17RA levels in GCP and GAP patients than in HS. Moreover, we found negative correlations between IL-23R in GT and probing depth and clinical attachment loss (CAL). Likewise, a positive correlation of IL-17RA in GT with CAL was found. Conclusions: The results of these findings suggest that the reverse behavior between IL-23R and IL-17RA in periodontitis patients may also be involved with the activation of RANKL, which promotes alveolar bone loss.

Activity of Cytokines and Expression of CD62L in Patients with Bronchial Asthma (기관지 천식환자에서 CD62L의 발현 및 싸이토카인의 변화)

  • Song, Kwang-Seon;Lee, Won-Yeon;Hong, Ae-Ra;Kim, Hee-Sun;Yong, Suk-Joong;Shin, Kye-Chul
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.1
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    • pp.90-98
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    • 1998
  • Background : The CD4+ T-helper cells comprise functionally distinct subsets of Th1 and Th2 cells that are distinguished on the basis of differential cytokines production Th1 cells secrete interferon-$\gamma$, lymphotoxin, interleukin-2. Th2 cells produce interleukin-4, interleukin-5, interleukin-10. A previous study shown that Th2 cells and their cytokines increased in patients with atopic asthma. We compared cytokines(IL-4, IFN-$\gamma$) activity and subpopulation of T-lymphocytes in peripheral blood from atopic asthmatics versus non-asthmatics. Method: Fifteen patients with atopic asthma(nine men, six women), twelve patients with chronic bronchitis(six men, six women), five healthy persons(three men, two women) were studied. Activity of IL-4, IFN-$\gamma$ and T-cell subpopulation in peripheral blood were estimated. Results: Patients had a median age of 55yr. The mean activity of IL-4 of asthmatics was significantly increased(control $0.75{\pm}1.1pmol/L$, atopic asthmatics $3.50{\pm}0.75pmol/L$, chronic bronchitis $2.01{\pm}1.2pmol/L$), but IFN-$\gamma$ was not significantly increased. In the T lymphocyte sunsets the percent of CD62L+ T-lymphoeytes of asthmatics was not significantly increased (control $16.7{\pm}16.4%$, atopic asthmatics $24.8{\pm}23.6%$, chronic bronchitis $17.0{\pm}16.9%$). Conclusion: In this study elevated production of IL-4 was observed in atopic asthmatics. CD62L+T-lymphoeytes was not increased in atopic asthma.

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Effect of Solvent Fractions from Doenjang on Antimutagenicity, Growth of Tumor Cells and Production of Interleukin-2 (된장 분획물의 항돌연변이 및 암세포 증식 억제효과와 interleukin-2 생성에 미치는 영향)

  • Kim, Kwang-Hyuk;Park, Kun-Young;Lee, Sook-Hee;Lim, Sun-Young
    • Journal of Life Science
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    • v.17 no.6 s.86
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    • pp.791-797
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    • 2007
  • We studied the inhibitory effect of solvent fractions from doenjang on mutagenicity using Salmonella typhimurium TA100 in Ames test. We also investigated the effect of solvent fractions from doenjang on the growth of tumor cells and the production of interleukin-2 (IL-2). The treatment of dichlorormethane and ethylacetate fractions (2.5 mg/assay) from doenjang to Ames test system inhibited aflatoxin B$_1$ (AFB$_1$) induced mutagenicity by 96% and 97%, respectively, and showed a higher antimutagenic effect than other solvent fractions. In case of N-methyl-N'-nitro-N-nitrosoguamidine (MNNG) induced mutagenicity, the ethylacetate fraction showed the highest inhibitory effect (by 75%) among the other sol-vent fractions, although the inhibitory effect was not stronger compared to AFB$_1$ induced mutagenicity. The treatment of dichloromethane and ethylacetate fractions markedly inhibited the growth of Yac-1 (by 80% and 94%, respectively) and sacroma-180 cancer cells (by 60% and 96%, respectively) after 4 days of incubation at 37${\circ}$C. To elucidate the immunological mechanism of antitumor activity of doenjang, spleen cells of Balb/c mouse were exposed to the dichloromethane and ethyl-acetate fractions for 24 hours at 37${\circ}$C . The culture supernatants following the treatment of djchloromethane and ethylacetate factions to spleen cells increased the production of IL-2. These results indicated that the anticarcinogenic effect of doenjang was mediated by the production of IL-2.