• Title/Summary/Keyword: anti CD40

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Effects of Mix-1 on Anti-CD40 Antibody and Recombinant IL4- Induced Cytokine Production and Immunoglobulin E in Highly Purified Mouse B Cells

  • Kim Jung Hwan;Choi Sun Mi;Lee Yong Gu;Namgoong Uk;Kim Dong Hee
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.6
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    • pp.1869-1880
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    • 2004
  • In the oriental medicine, a mixture of herbs has been commonly used as important components to control allergic and inflammatory diseases. In the present study, we prepared a mixture of Dictamni Radicis Cortex(Baiksunpee), Houttuyniae Herba(Uhsungcho), and Aurantii Immaturus Fructus(Jisil) to examine its anti-allergic effects in activated mouse splenic cells and found that Mix-1 is involved in regulating levels of B cell activating factors (CD23 and CD11a), IL-1β, IL-6, IL-10, TNF-α, and 1gE as well as HRF expression. It was observed that Mix-1 did not have cytotoxic effects on mLFC. Mix-1 showed inhibition of CD23 and CD11 alpaha expression in mouse B cells, and also decreased the production of IL-6, TNF-α, and 1gE. Both RT-PCR and ELISA analyses indicated that IL-6 and TNF alpha production were regulated at the gene expression level. In contrast, IL-10 mRNA and protein levels were increased in activated B cells by Mix-1 treatment. We also found that Mix-1 inhibited B cell proliferation and inhibited histamine releasing factor(HRF) expression, suggesting its inhibitory effect on histamine secretion. These data indicated that Mix-1 has an anti-allergic effect in activated macrophages and further suggest the possible application of Mix-1 as a therapeutic agent for the treatment of allergy-related diseases.

Interleukin-7 Enhances the in Vivo Anti-tumor Activity of Tumor-reactive CD8+ T cells with Induction of IFN-gamma in a Murine Breast Cancer Model

  • Yuan, Chun-Hui;Yang, Xue-Qin;Zhu, Cheng-Liang;Liu, Shao-Ping;Wang, Bi-Cheng;Wang, Fu-Bing
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.1
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    • pp.265-271
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    • 2014
  • Interleukin-7 (IL-7) is a potent anti-apoptotic cytokine that enhances immune effector cell functions and is essential for lymphocyte survival. While it known to induce differentiation and proliferation in some haematological malignancies, including certain types of leukaemias and lymphomas, little is known about its role in solid tumours, including breast cancer. In the current study, we investigated whether IL-7 could enhance the in vivo antitumor activity of tumor-reactive $CD8^+$ T cells with induction of IFN-${\gamma}$ in a murine breast cancer model. Human IL-7 cDNA was constructed into the eukaryotic expression plasmid pcDNA3.1, and then the recombinational pcDNA3.1-IL-7 was intratumorally injected in the TM40D BALB/C mouse graft model. Serum and intracellular IFN-${\gamma}$ levels were measured by ELISA and flow cytometry, respectively. $CD8^+$ T cell-mediated cytotoxicity was analyzed using the MTT method. Our results showed that IL-7 administration significantly inhibited tumor growth from day 15 after direct intratumoral injection of pcDNA3.1-IL-7. The anti-tumor effect correlated with a marked increase in the level of IFN-${\gamma}$ and breast cancer cells-specific CTL cytotoxicity. In vitro cytotoxicity assays showed that IL-7-treatment could augment cytolytic activity of $CD8^+$ T cells from tumor bearing mice, while anti-IFN-${\gamma}$ blocked the function of $CD8^+$ T cells, suggesting that IFN-${\gamma}$ mediated the cytolytic activity of $CD8^+$ T cells. Furthermore, in vivo neutralization of $CD8^+$ T lymphocytes by CD8 antibodies reversed the antitumor benefit of IL-7. Thus, we demonstrated that IL-7 exerts anti-tumor activity mainly through activating $CD8^+$ T cells and stimulating them to secrete IFN-${\gamma}$ in a murine breast tumor model. Based on these results, our study points to a potential novel way to treat breast cancer and may have important implications for clinical immunotherapy.

Experimental Study on Anti-allergic and Anti-inflammatory Effects of Soeumin-Googwihyangso-san Methanol Extract in Vitro (소음인(少陰人) 궁귀향소산(芎歸香蘇散)의 항(抗) 알레르기 및 항(抗) 염증에 미치는 실험적 연구)

  • Nam, Sang-Choon;Kang, Hee;Shim, Bum-Sang;Kim, Sung-Hoon;Choi, Seung-Hoon;Ahn, Kyoo-Seok
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.1
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    • pp.41-49
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    • 2009
  • Soeumin-Googwihyangso-san(SGGHSS) has been used for the prevention or treatment of Soeumin-allergic rhinitis. This study was performed to demonstrate anti-allergic and anti-inflamatory effects of SGGHSS methanol extract in HMC cell lines and activated mouse B cells and CD4+ T cells. SGGHSS inhibited the production of TNF-$\alpha$ in PMA plus A23187 activated HMC-1 cells but not that of IL-6, as measured by ELISA. SGGHSS inhibited the expression of CD23 and surface IgE in B cells as determined by flowcytometry. It also inhibited secretion of IFN-$\gamma$ and IgG1, the Th1 related IgG type, but increased that of IL-4 in anti-CD40 and IL-4 treated B cells as measured by ELISA. As for Th cell differentiation, SGGHSS did not much affect IL-4 or IFN-$\gamma$. Taken together, our data showed that SGGHSS exerted an anti-inflammtory effect by inhibiting TNF-$\alpha$ in mast cells and has anti-allergic activity not via inhibition of CD4+ T cell, but via inhibition of B cells. These results suggest some evidence that SGGHSS can be applied to allergic disease.

Effect of Kami-Cheongsimyeonjatang on cytokine expression with GATA3 regulation in atopic dermatitis-like skin lesions and IgE hyperproduction induced in NC/Nga mice (IgE 과대생산과 피부염이 유발된 NC/Nga생쥐의 비장세포에서 GATA3 조절에 의한 유전자 발현에 미치는 영향)

  • Park, Seul-Ki;Han, Jae-Kyung;Kim, Yun-Hee
    • Journal of Haehwa Medicine
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    • v.17 no.2
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    • pp.167-183
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    • 2008
  • KCSYJT medicines controlled $CD4^+/IFN-\gamma$, and $CD4^+/CD25^+/foxp3^+$ revelation that an experiment that motive allergy immune reponse because an in vitro experiment stimulates T cells of a NC/Nga mouse same time by anti-CD40/rmIL-4, and interleukin-$1{\beta}$, IL-6, TNF-$\alpha$, and TGF-$\beta$ mRNA outturn that bear in T and B cells decreased remarkably by KCSYJT medicines. Intracellular staining of splenocytes anti-CD40/rmIL-4 plus rmIL-4 stimulated as described in a, assessed after 24 h, KCSYJT exerts a mainly immunosuppressive effect that acts at least partially through suppression of the transcription factor GATA3 expression in $CD4^+$ T cells. We found that skin lesions, which were clinically and histologically very similar to human AD, mite antigen-induced dermatitis on the face, neck, ears and dorsal skin of inbred NC/Nga mice. Result that Th1 cell and Th2 cell observe to be shifted by cytokine expression with GATA3 regulation by KCSYJT medicines could know that KCSYJT medicines can use usefully in allergy autoimmnune diease.

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Effects of Naenghyohwan(NHH) on anti-CD40 and rIL-4 induced cytokine production and IgE, Histamine in highly purified mouse B cells (생쥐의 B세포(細胞)에서 anti-CD40과 rIL-4로 유도된 Cytokine 생산과 IgE, Histamine에 대한 냉효환(冷哮丸)의 효과(效果))

  • Yoo, Seon-Woong;Park, Yang-Chun
    • The Journal of Internal Korean Medicine
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    • v.25 no.2
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    • pp.245-257
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    • 2004
  • This study was done to evaluate the antiallergic effects of Naenghyohwan(NHH). Cytotoxic activity for lung fibroblast cells, cytokines transcript expression of IL-1, IL-4, IL-5, TNF-${\alpha}$, IL-6, IL-10, TGF-${\beta}$1, IFN-${\gamma}$, production of IL-4, IL-10. IFN-${\gamma}$, IgE in anti-CD40mAb plus rIL-4 stimulated murine splenic B cells and the production of histamin released in mast cells, and the expression of histamine release factor(HRF) in splenic B cells were measurd. The following results were obtained. NHH did not showed cytotoxicity in fibroblast cells. NHH increased the gene synthesis of TNF-${\alpha}$, IFN-${\gamma}$(m-RNA). NHH decreased the gene synthesis of IL-1${\beta}$, IL-4, IL-5, IL-6, TGF-${\beta}1$(m-RNA). NHH decreased the appearance of IL-4, IgE significantly. NHH increased the appearance of IL-10. IFN-${\gamma}$ significantly. NHH decreased the proliferation of B cells significantly. NHH decreased the appearance of histamin expression of HRF in mast cells significantly. The results suggest NHH is effective against the allergies. Continued studies of the antiallergic effects of NHH are urged.

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Antioxidant, anti-inflammatory, and antimicrobial activity of hesperetin and its cyclodextrin inclusion complexes (헤스페레틴(Hesperetin)과 사이클로덱스트린(Cyclodextrin) 포접 복합체의 항산화, 항염증, 항균 활성 )

  • Sung-Sook Choi;Kyung-Ae Lee
    • Journal of the Korean Applied Science and Technology
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    • v.40 no.5
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    • pp.988-1000
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    • 2023
  • Hesperetin(HT) is a potent antioxidant flavonoid aglycone derived from hesperidin(HD). The antioxidant, anti-inflammatory, and antimicrobial activities of HT and its cyclodextrin(CD) inclusion complexes were compared in vitro. HT was prepared by enzymatic hydrolysis of HD, and HT/CD complexes were prepared using 𝛽-cyclodextrin(𝛽-CD) and hydroxypropyl-𝛽-cyclodextrin(HP-𝛽-CD) by solvent co-evaporation method. The solubility of the HT/HP-𝛽-CD inclusion complex increased 93.5-fold compared to HT, and the solubility of HT/𝛽-CD increased 22.5-fold. The HT/HP-𝛽-CD inclusion complex showed a similar effect as HT on radical scavenging activity in antioxidant assays, whereas the HT/𝛽-CD inclusion complex showed slightly lower activity than HT. Cytotoxicity was low in the following order; HT/HP-𝛽-CD, HT/𝛽-CD, and HT in murine macrophage RAW264.7 cells. Treatment with HT and HT/CD inclusion complexes reduced the levels of inflammatory mediators such as nitric oxide(NO), tumor necrosis factor-𝛼(TNF-𝛼) and interleukin-6(IL-6) in the cells. HT and HT/HP-𝛽-CD inclusion complex were more effective than HT/𝛽-CD inclusion complex at relatively low concentrations. Inhibitory effects were tested on skin-pathogenic bacteria, Staphylococcus aureus and Pseudomonas aeruginosa, and they showed an antimicrobial effect on S. aureus in the order of HT = HT/HP-𝛽-CD > HT/𝛽-CD, but they did not show any significant inhibitory effect on P. aeruginosa. In conclusion, HT, the aglycone form of HD, and its CD inclusion complexes showed various biological activities. HT/HP-𝛽-CD inclusion complex, which is the highly soluble form of HT, showed relatively higher activity compared to HT/𝛽-CD inclusion complex.

Medication Use and Drug Expenditure in Inflammatory Bowel Disease: based on Korean National Health Insurance Claims Data (2010-2014) (국내 염증성장질환의 약물치료 및 약제비 현황: 2010-2014 국민건강보험자료 활용 연구)

  • Ha, Jung Eun;Jang, Eun Jin;Im, Seul Gi;Sohn, Hyun Soon
    • Korean Journal of Clinical Pharmacy
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    • v.29 no.2
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    • pp.79-88
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    • 2019
  • Backgrounds: Inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn's disease (CD) increased prevalence and economic burden. Objectives: This study aimed to investigate drug use pattern in IBD patients in a real world. Methods: National Health Insurance claim data from 2010 to 2014 were used in this population-based study. All IBD patients diagnosed during study period were enrolled. IBD medications included 5-aminosalicylic acid (ASA), glucocorticoid, immunomodulator and anti-tumor necrosis factor-${\alpha}$ agent(anti TNF-${\alpha}$). Growth rate of IBD prevalence, prescribed drug classes, duration of drug therapy and medication cost were analyzed. Number and percentage of patients for categorical variables, and mean and median for continuous variables were presented. Results: Total numbers of patients were 131,158 and 57,286 during 5 years, and their annual growth rate were 3.2 and 5.7% for UC and CD. UC and CD were prevalent in the 40-50 (41.2%) and 20-30 age groups (36.0%). About 60% of IBD patients was prescribed any of medications. 5-ASA was the most frequently prescribed, followed by corticosteroid and immunomodulator. Anti TNF-${\alpha}$ use was the lowest, but 5 times higher than UC in CD. Combination therapies with different class of drugs were in 29% for UC and 62% for CD. Mean prescription days per patient per year were 306 and 378, and the median medication cost per patient per year was KRW 420,000 (USD 383) and KRW 830,000 (USD755), for UC and CD, respectively. Conclusions: Increasing prevalence of IBD requires further studies to contribute to achieve better clinical outcomes of drug therapy.

EFFECTS OF MACROPHAGE INFLAMMATORY $PROTEIN-1{\alpha}$ON THE T CELL PROLIFERATION AND THE EXPRESSION OF CD4 AND CD8 (Macrophage Inflammatory Protein $1{\alpha}$가 T세포성장 및 CD4, CD8 발현에 미치는 영향)

  • Choi, Jong-Sun;Kim, Oh-Whan
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.18 no.1
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    • pp.153-163
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    • 1996
  • Macrophage inflammatory protein $(MIP)-1{\alpha}$ is a cytokine which produces wide range of bioactivities such as proinflammatory, immunomodulatory, and hematopoietic modulatory actions. To determine whether $MIP-1{\alpha}$ acts as a negative regulator on the functions of lymphocyte, $[^3H]$-thymidine incorporation test and flow cytometric analysis were performed by using human tonsil T cell, human peripheral blood T cell, and murine cytolytic T lymphocyte (CTL) line CTLL-2, The results were as follow. 1. When human tonsil T lymphocytes were stimulated with anti-CD3 monoclonal antibody (mAb), rate of T cell proliferation was about four times increased. 200ng/ml of $MIP-1{\alpha}$ inhibited anti-CD3 mAb-mediated T cell growth as much as 60% (P<0.05). 2. The suppression of human peripheral T cell proliferation produced by $MIP-1{\alpha}$ was dramatic, but variable among T cells derived from different individuals $(40%{\sim}90%)$. 3. $MIP-1{\alpha}$inhibited the proliferation of murine CTL line CTLL-2 as much as 75%(P<0.001). 4. When the $MIP-1{\alpha}$ was added to human peripheral T cell, cell proporation of $CD4^+$ helper T cell and $CD8^+$ CTL were not noticeably affected. The expression level of CD4, not of Cd8, however, was down regulated by $MIP-1{\alpha}$ treatment $(27%{\sim}82%)$.

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Characterization of B Cells of Lymph Nodes and Peripheral Blood in a Patient with Hyper IgM Syndrome (Hyper IgM Syndrome 환자에서 얻은 림프절 및 말초혈액 B세포의 특성)

  • Kim, Dong Soo;Shin, Kyuong Mi;Yang, Woo Ick;Shin, Jeon-Soo;Song, Chang Hwa;Jo, Eun Kyeong
    • Clinical and Experimental Pediatrics
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    • v.46 no.2
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    • pp.128-136
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    • 2003
  • Purpose : Hyper IgM syndrome(HIGM) is characterized by severe recurrent bacterial infections with decreased serum levels of IgG, IgA, and IgE but elevated IgM levels. Recently, it has been classified into three groups; HIGM1, HIGM2 and a rare form of HIGM. HIGM1 is a X-linked form of HIGM and has now been identified as a T-cell deficiency in which mutations occur in the gene that encodes the CD40 ligand molecule. HIGM2 is an autosomal recessive form of HIGM. Molecular studies have shown that the mutation of HIGM2 is in the gene that encodes activation-induced cytidine deaminase(AID). Recently, another rare form of X-linked HIGM syndrome associated with hypohydrotic ectodermal dysplasia has been identified. We encountered a patient with a varient form of HIGM2. To clarify the cause of this form of HIGM, we evaluated the peripheral B cells of this patient. Methods : The lymphocytes of the patient were prepared from peripheral blood. B cells were immortalized with the infection of EBV. Cell cycle analysis was done with the immortalized B cells of the patient. Peripheral mononuclear cells were stained with monoclonal anti-CD40L antibody. Total RNA was extracted from the peripheral mononuclear cells. After RT-PCR, direct sequencing for CD40L gene and HuAID gene were done. Immunostainings of a lymph node for CD3, CD23, CD40, Fas-L, bcl-2, BAX were done. Results : The peripheral B cells of this patient showed normal expression of CD40L molecule and normal sequencing of CD40L gene, and also normal sequencing of AID gene. Interestingly, the peripheral B cells of this patient showed a decreased population of G2/mitosis phase in cell cycles which recovered to normal with the stimulation of IL-4. Conclusion : We suspect that the cause of increased serum IgM in this patient may be from a decrease of G2/mitosis phase of the peripheral B cells, which may be from the decreased production or secretion of IL-4. Therefore, this may be a new form of HIGM.

Effect of SoPungDoJeokTang-KaMi on cytokine expression with $CD4^+/CD25^+/foxp3^+$ (Treg) cell induction in atopic dermatitis-like skin lesions and IgE hyperproduction induced in NC/Nga mice (소풍도적탕가미(消風導赤湯加味)가 IgE 과대생산과 피부염이 발진된 NC/Nga생쥐의 비장세포에서 $CD4^+/CD25^+/foxp3^+$ Treg 증진에 의한 유전자 발현에 미치는 영향)

  • Han, Dal-Soo;Han, Jae-Kyung;Kim, Yun-Hee
    • Journal of Haehwa Medicine
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    • v.18 no.1
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    • pp.29-41
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    • 2009
  • Wished to examine closely effect that SoPungDoJeokTang-KaMi (SPDJTK) medicines used to atopy dermatitis disease patient get in atopy eruption control experimentally. SPDJTK medicines controlled $CD4^+/IFN-\gamma$, and $CD4^+/CD25^+/foxp3^+$ revelation that an experiment that motive allergy immune reponse because an in vitro experiment stimulates T cells of a NC/Nga mouse same time by anti-CD40/rmIL-4, and interleukin-$1{\beta}$, IL-6, TNF-$\alpha$, and TGF-$\beta$ mRNA outturn that bear in T and B cells decreased remarkably by SPDJTK medicines. Intracellular staining of splenocytes anti-CD40/rmIL-4 plus rmIL-4 stimulated as described in a, assessed after 24 h, SPDJTK exerts a mainly immunosuppressive effect that acts at least partially through suppression of the transcription factor GATA3 expression in $CD4^+$ T cells. Atopic dermatitis (AD) usually develops in patients with an individual or family history of allergic diseases, and is characterized by chronic relapsing inflammation seen specially in childhood, association with IgE hyperproduction and precipitation by environmental factors. However, the exact etiology of AD has been unclear. To further explore the pathogenesis and treatment of AD, a suitable animal model is required. We found that skin lesions, which were clinically and histologically very similar to human AD, mite antigen-induced dermatitis on the face, neck, ears and dorsal skin of inbred NC/Nga mice. Result that Th1 cell and Th2 cell observe to be shifted by cytokine expression with $CD4^+/CD25^+/foxp3^+$ Treg cells induction by SPDJTK medicines could know that SPDJTK medicines can use usefully in allergy autoimmnune diease.

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