• Title/Summary/Keyword: immune tolerance

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Dietary Aloe Improves Insulin Sensitivity via the Suppression of Obesity-induced Inflammation in Obese Mice

  • Shin, Eun-Ju;Shim, Kyu-Suk;Kong, Hyun-Seok;Lee, Sung-Won;Shin, Seul-Mee;Kwon, Jeung-Hak;Jo, Tae-Hyung;Park, Young-In;Lee, Chong-Kil;Kim, Kyung-Jae
    • IMMUNE NETWORK
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    • v.11 no.1
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    • pp.59-67
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    • 2011
  • Background: Insulin resistance is an integral feature of metabolic syndromes, including obesity, hyperglycemia, and hyperlipidemia. In this study, we evaluated whether the aloe component could reduce obesity-induced inflammation and the occurrence of metabolic disorders such as blood glucose and insulin resistance. Methods: Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of aloe formula (PAG, ALS, Aloe QDM, and Aloe QDM complex) or pioglitazone (PGZ) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. Results: Aloe QDM lowered fasting blood glucose and plasma insulin compared with HFD. Obesity-induced inflammatory cytokine (IL-$1{\beta}$, -6, -12, TNF-${\alpha}$) and chemokine (CX3CL1, CCL5) mRNA and protein were decreased markedly, as was macrophage infiltration and hepatic triglycerides by Aloe QDM. At the same time, Aloe QDM decreased the mRNA and protein of $PPAR{\gamma}/LXR{\alpha}$ and $11{\beta}$-HSD1 both in the liver and WAT. Conclusion: Dietary aloe formula reduces obesity-induced glucose tolerance not only by suppressing inflammatory responses but also by inducing anti-inflammatory cytokines in the WAT and liver, both of which are important peripheral tissues affecting insulin resistance. The effect of Aloe QDM complex in the WAT and liver are related to its dual action on $PPAR{\gamma}$ and $11{\beta}$-HSD1 ression and its use as a nutritional intervention against T2D and obesity-related inflammation is suggested.

Globular Adiponectin Exerts a Pro-Inflammatory Effect via IκB/NF-κB Pathway Activation and Anti-Inflammatory Effect by IRAK-1 Downregulation

  • Lee, Kyoung-Hee;Jeong, Jiyeong;Woo, Jisu;Lee, Chang-Hoon;Yoo, Chul-Gyu
    • Molecules and Cells
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    • v.41 no.8
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    • pp.762-770
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    • 2018
  • Adiponectin, a hormone produced by adipose tissue, is very abundant in plasma, and its anti- and pro-inflammatory effects are reported. However, the mechanisms of these pro- and anti-inflammatory effects are not fully defined. Herein, we evaluated the dual inflammatory response mechanism of adiponectin in macrophages. Short-term globular adiponectin (gAd) treatment induced $I{\kappa}B{\alpha}$ degradation, $NF-{\kappa}B$ nuclear translocation, and $TNF-{\alpha}$ production in RAW 264.7 cells. Polymyxin B pretreatment did not block gAd-induced $I{\kappa}B{\alpha}$ degradation, and heated gAd was unable to degrade $I{\kappa}B{\alpha}$, suggesting that the effects of gAd were not due to endotoxin contamination. gAd activated IKK and Akt, and inhibition of either IKK or Akt by dominant-negative $IKK{\beta}$ ($DN-IKK{\beta}$) or DN-Akt overexpression blocked gAd-induced $I{\kappa}B{\alpha}$ degradation, suggesting that short-term incubation with gAd mediates inflammatory responses by activating the $I{\kappa}B/NF-{\kappa}B$ and PI3K/Akt pathways. Contrastingly, long-term stimulation with gAd induced, upon subsequent stimulation, tolerance to gAd, lipopolysaccharide, and CpG-oligodeoxynucleotide, which is associated with gAd-induced downregulation of IL-receptor-associated kinase-1 (IRAK-1) due to IRAK-1 transcriptional repression. Conclusively, our findings demonstrate that the pro- and anti-inflammatory responses to gAd in innate immune cells are time-dependent, and mediated by the activation of the $I{\kappa}B/NF-{\kappa}B$ pathway, and IRAK-1 downregulation, respectively.

The importance of clinical mistletoe cancer therapy and korean mistletoe pharmacopuncture preparation development and application possibility for oriental medicine (겨우살이 암치료제의 임상의학적 중요성과 한의학적 겨우살이 약침제제 개발 및 적용 가능성에 관한 고찰)

  • Choi, Ok-Byung
    • Journal of Pharmacopuncture
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    • v.12 no.1
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    • pp.77-89
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    • 2009
  • Objectives : Mistletoe extracts have been in use for around 85 years, predominantly in the area of cancer therapy. Today mistletoe preparations are among the most prescribed drugs in cancer medicine, thus constituting a standard biological therapy in the area of oncology. The purpose of this study is to analyze the practical implications of mistletoe cancer therapy, their clinical status, their preparation techniques and companies. Contents : Mistletoe therapy for cancer has been developed within the context of anthroposophical medicine. One major effect of mistletoe extract is that it stimulates the immune system and cancer defences. In Germany, a total of eight different mistletoe preparations are available, five developed by Anthroposophic Medicine and three evolved from research in phytotherapy. Therapy always consists of an introductory phase in order to test the patient's tolerance, find the right dosage and choose the most suitable preparation. This paper covers the background of mistletoe medical plant materials, mistletoe therapy for cancer, the anthroposophical medicine and clinical research, the practical regulation of treatment, preparation of mistletoe drugs. Result & suggestion : Mistletoe extracts are a complementary teratment of cancer, widely used in intergrative cancer care. The study of the integration of korean mistletoe extracts to oriental cancer medicine, its development and feasibility in Korea are urgently needed. The products, substances, compositions of european mistletoe drugs are very similar to those of oriental medicine theory. Applying the mistletoe cancer therapy and its preparation techniques to oriental medicine, the herbal acupuncture preparation should be modernized and korean mistletoe products are to be developed. To this end, government and herbal acupuncture society need to interact each other for the development of oriental mistletoe cancer medicine.

Identification of ABSCISIC ACID (ABA) signaling related genes in Panax ginseng

  • Hong, Jeongeui;Kim, Hogyum;Ryu, Hojin
    • Journal of Plant Biotechnology
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    • v.45 no.4
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    • pp.306-314
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    • 2018
  • Korean ginseng (Panax ginseng) has long been cultivated as an important economic medicinal plant. Owing to the seasonal and long-term agricultural cultivation methods of Korean ginseng, they are always vulnerable to various environmental stress conditions. ABSCISIC ACID (ABA) is an essential plant hormone associated with seed development and diverse abiotic stress responses including drought, cold and salinity stress. By modulating ABA responses, plants can regulate their immune responses and growth patterns to increase their ability to tolerate stress. With recent advances in genome sequencing technology, we first reported the functional features of genes related to canonical ABA signaling pathway in P. ginseng genome. Based on the protein sequences and functional genomic analysis of Arabidopsis thaliana, the ABA related genes were successfully identified. Our functional genomic characterizations clearly showed that the ABA signaling related genes consisting the ABA receptor proteins (PgPYLs), kinase family (PgSnRKs) and transcription factors (PgABFs, PgABI3s and PgABI5s) were evolutionary conserved in the P. ginseng genome. We confirmed that overexpressing ABA related genes of P. ginseng completely restored the ABA responses and stress tolerance in ABA defective Arabidopsis mutants. Finally, tissue and age specific spatio-temporal expression patterns of the identified ABA-related genes in P. ginseng tissues were also classified using various available RNA sequencing data. This study provides ABA signal transduction related genes and their functional genomic information related to the growth and development of Korean ginseng. Additionally, the results of this study could be useful in the breeding or artificial selection of ginseng which is resistant to various stresses.

Using Ivermectin for treating channel catfish (Ictalurus punctatus) infected with Dollfustrema bagarii

  • Manh Duc Vu;Kim Minh Anh;Lua Thi Dang;Hung Manh Nguyen;Trinh Tran Thi;Nhinh Doan Thi;Manh Van Ngo;Kim Van Van
    • Fisheries and Aquatic Sciences
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    • v.27 no.9
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    • pp.614-621
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    • 2024
  • Channel catfish (Ictalurus punctatus), an introduced species in Vietnam, is widely cultured in the Northern provinces. The off-white grub disease in Channel catfish, caused by metacercariae of Dollfustrema bagarii (Digenea: Bucephalidae) lodged in internal organs, often results in heavy economic losses. Up to the present, there have been no specific guidelines for preventing and treating this disease. Here, we explore the potential treatment of infected channel catfish through the injection of Ivermectin. We evaluated the tolerance of channel catfish to the drug and determined the optimal dosage for treating off-white grubs disease. Healthy fish weighing 180-200 g received dosages of up to 3.250 mg/kg of body weight. The median lethal dose (LD50) throughout a 24-hour period was 0.808 mg/kg body weight, with a confidence interval ranging from 0.583 to 1.118 mg/kg body weight. The infected fish used for treatment testing ranged in weight from 400 to 500 g. The value for the 24-hour median effective dose (ED50) was 0.253 mg, and the appropriate therapeutic injection ranged from 0.300 to 0.700 mg per kg of body weight. Flowing the histopathological alterations, after the metacercariae were shriveled and died, the immune cells cleaned and eliminated them from fish.

Expression of COX-2 and IDO by Uteroglobin Transduction in NSCLC Cell Lines (비소세포폐암 세포주에서 Uteroglobin Transduction이 COX-2 및 IDO의 발현에 미치는 영향)

  • Park, Gun Min;Lee, Sang-Min;Yim, Jae-Joon;Yang, Seok-Chul;Yoo, Chul Gyu;Lee, Choon-Taek;Han, Sung Koo;Sim, Young-Soo;Kim, Young Whan
    • Tuberculosis and Respiratory Diseases
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    • v.66 no.4
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    • pp.274-279
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    • 2009
  • Background: Uteroglobin (UG) is a secretary protein that has strong immunomodulatory properties, and which is synthesized in most epithelia including lung tissue. Overexpression of UG is associated with decreased expression of cyclooxygenase (COX)-2 and suppression of cancer cell growth. Indoleamine 2,3-dioxygenase (IDO) catalyzes tryptophan along the kynurenine pathway, and both the reduction in local tryptophan and the production of tryptophan metabolites contribute to the immunosuppressive effects of IDO. Methods: In this study, we investigated the pattern of expression of COX-2 and IDO, and the effect of UG transduction in the expression of COX-2 and IDO in several non-small cell lung cancer cell lines, especially A549. Results: Both COX-2 and IDO were constitutionally expressed in A549 and H460 cells, and was reduced by UG transduction. In A549 cells, the slightly increased expression of COX-2 and IDO with the instillation of interferon-gamma (IFN-$\gamma$) was reduced by UG transduction. However, the reduced expression of COX-2 and IDO by UG transduction was not increased with IFN-$\gamma$ instillation in A549 cells. In both the A549 COX-2 sense and the A549 COX-2 anti-sense small interfering RNA (siRNA)-transfected cells, IDO was expressed; expression was reduced by UG transduction, irrespective of the expression of COX-2. Conclusion: The results suggest that the anti-proliferative function of UG may be associated with the immune tolerance pathway of IDO, which is independent of the COX-2 pathway.

Inhibition of Graft Versus Host Disease Using CD4+CD25+ T Cells Induced with Interleukin-2 in Mismatched Allogeneic Murine Hematopoietic Stem Cell Transplantation (주조직적합항원이 불일치하는 마우스 동종 조혈모세포이식에서 IL-2로 유도된 CD4+CD25+ T세포를 이용한 이식편대숙주병의 억제)

  • Hyun, Jae Ho;Jeong, Dae Chul;Chung, Nak Gyun;Park, Soo Jeong;Min, Woo Sung;Kim, Tai Gyu;Choi, Byung Ock;Kim, Won Il;Han, Chi Wha;Kim, Hack Ki
    • IMMUNE NETWORK
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    • v.3 no.4
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    • pp.287-294
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    • 2003
  • Background: In kidney transplantation, donor specific transfusion may induce tolerance as a result of some immune regulatory cells against the graft. In organ transplantation, the immune state arises from a relationship between the immunocompromised graft and the immunocompetent host. However, a reverse immunological situation exists between the graft and the host in hematopoietic stem cell transplantation (HSCT). In addition, early IL-2 injections after an allogeneic murine HSCT have been shown to prevent lethal graft versus host disease (GVHD) due to CD4+ cells. We investigated the induction of the regulatory CD4+CD25+ cells after a transfusion of irradiated recipient cells with IL-2 into a donor. Methods: The splenocytes (SP) were obtained from 6 week-old BALB/c mice ($H-2^d$) and irradiated as a single cell suspension. The donor mice (C3H/He, $H-2^k$) received $5{\times}10^6$ irradiated SP, and 5,000 IU IL-2 injected intraperitoneally on the day prior to HSCT. The CD4+CD25+ cell populations in SP treated C3H/He were analyzed. In order to determine the in vivo effect of CD4+CD25+ cells, the lethally irradiated BALB/c were transplanted with $1{\times}10^7$ donor BM and $5{\times}10^6$ CD4+CD25+ cells. The other recipient mice received either $1{\times}10^7$ donor BM with $5{\times}10^6$ CD4+ CD25- cells or the untreated SP. The survival and GVHD was assessed daily by a clinical scoring system. Results: In the MLR assay, BALB/c SP was used as a stimulator with C3H/He SP, as a responder, with or without treatment. The inhibition of proliferation was $30.0{\pm}13%$ compared to the control. In addition, the MLR with either the CD4+CD25+ or CD4+CD25- cells, which were isolated by MidiMacs, from the C3H/He SP treated with the recipient SP and IL-2 was evaluated. The donor SP treated with the recipient cells and IL-2 contained more CD4+CD25+ cells ($5.4{\pm}1.5%$) than the untreated mice SP ($1.4{\pm}0.3%$)(P<0.01). There was a profound inhibition in the CD4+CD25+ cells ($61.1{\pm}6.1%$), but a marked proliferation in the CD4+CD25- cells ($129.8{\pm}65.2%$). Mice in the CD4+CD25+ group showed low GVHD scores and a slow progression from the post-HSCT day 4 to day 9, but those in the control and CD4+CD25- groups had a high score and rapid progression (P<0.001). The probability of survival was 83.3% in the CD4+CD25+ group until post-HSC day 35 and all mice in the control and CD4+CD25- groups died on post-HSCT day 8 or 9 (P=0.0105). Conclusion: Donor graft engineering with irradiated recipient SP and IL-2 (recipient specific transfusion) can induce abundant regulatory CD4+CD25+ cells to prevent GVHD.

Recent Studies on the Edible Plant Vaccine for Prophylactic Medicine against Microorganism-Mediated Diseases (세균성 질병 예방을 위한 식물 경구 백신 연구 동향)

  • Hahn Bum-Soo;Jeong Young-Jae;Roh Kyung-Hee;Park Jong-Sug;Cho Kang-Jin;Kim Yong-Hwan;Kim Jong-Bum
    • Journal of Plant Biotechnology
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    • v.32 no.4
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    • pp.233-241
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    • 2005
  • Plants have considerable advantages for the production of antigenic proteins because they provide an inexpensive source of protein and an easy administration of vaccine. Since a publication describing edible plant vaccine of HBsAg in 1992, a number of laboratories around the world have studied the use of plants as the bioreactor to produce antigenic proteins of human or animal pathogens. Over the last ten years, these works have been mainly focused on three major strategies for the production of antigenic proteins in plants: stable genetic transformation of either the nuclear or plastid genome, or transient expression in plants using viral vectors. As many antigenic proteins have been expressed in tobacco, also several laboratories have succeeded to express genes encoding antigenic proteins in other crop plants: potato, tomato, maize, carrot, soybean and spinach. At present many works for the production of edible plant vaccine against bacteria-mediated diseases have mostly performed the studies of enterotoxins and adhesion proteins. Also the development of new-type antigens (pili, flagella, surface protein, other enterotoxin and exotoxin etc.) is required for various targets and more efficacy to immunize against microorganism pathogens. Many works mostly studied in experimental animals had good results, and phase I clinical trial of LTB clearly indicated its immunogenic ability. On the other hand, edible plant vaccines have still problems remained to be solved. In addition to the accumulation of sufficient antigen in plants, human health, environment and agriculture regulation should be proven. Also oral tolerance, the physiological response to food antigens and commensal flora is the induction of a state of specific immunological unresponsiveness, needs to be addressed before plant-derived vaccine becomes a therapeutic option.

The current status of fumonisin toxicosis in domestic animals: A review (가축의 fumonisin 중독증에 대한 최근 연구 동향 : 종설)

  • Lim, Chae-woong;Rim, Byung-moo
    • Korean Journal of Veterinary Research
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    • v.35 no.2
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    • pp.405-416
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    • 1995
  • FBs, secondary metabolites of several species of Fusaria, especially Fusarium moniliforme and F proliferatum, are commonly contaminated in com and other food grains throughout the world. Only recently identified, these mycotoxins have been associated field outbreaks of ELEM in horses and PPE in pigs. Currently, naturally or experimentally induced FB toxicosis has been studied in poultry, ruminants and rabbits. Poultry fed FB showed decreased growth rate, performance, and immune competence, as well as embryopathic, and embryocidal effects, and ricktes. Ruminants seem to be relatively less susceptible to FBs than other doestic animal. FB toxicosis reveals that liver is a target organ in all species, although other organs are affected in a species specific manner. Recently, the main target organs for $FB_1$ toxicity in rabbits was shown to be the kidney. Even low concentrations of FBs are likely to be a problem for animal health. A current study being conducted showed that feed containing low level of $FB_1$ reduces the ability of pulmonary intravascular macrophages in pig to clear blood-borne particles which would increase the susceptibility of animals to bacterial disease. The mechanism of FB toxicity remains unknown, but may be related to altered sphingolipid biosynthesis by inhibiting sphinganine N-acyltransferase. Elevations of serum and tissue SA:SO ratio have been observed in horse, pig, chicken, turkey, and rabbit, which could could serve as in effective biomarker for consumption of FB-containing feeds. There is limited information detailing dose-effect relationships either from field cases or in the laboratory. More research on the factors, including the prevalence and tolerance levels of FBs in feedstuffs that cause domestic animal disease associated with FBs, is urgently needed.

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Current Status of Face Transplantation: Where Do We Stand in Korea? (안면이식에 대한 최근 동향: 한국에서의 안면이식은 어떤 단계에 있는가?)

  • Hong, Jong Won;Kim, Young Seok;Yun, In Sik;Lee, Dong Won;Lee, Won Jai;Roh, Tai Suk;Lew, Dae Hyun;Kim, Yong Oock;Rah, Dong Kyun;Tark, Kwan Chul;Yun Park, Be-Young
    • Archives of Craniofacial Surgery
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    • v.13 no.2
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    • pp.85-94
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    • 2012
  • The world's first face transplantation was performed in France, in 2005. Since then, 21 cases of face transplantation have been performed. Face transplantation is one of the most prominent part of composite tissue allotransplantation (CTA) along with hand transplantation. Since these fields are not deal with life-saving organs, there are many arguments about immunosuppression therapy. Recent paradigm of face transplantation shows that surgical ranges are expanded from partial face transplantation to full face transplantation. Most immunosuppression protocols are triple therapy, which consists of tacrolimus (FK-506), mycophenolate mofetil and prednisolone. Anatomical researches, immunosuppression, and immunotolerance take great parts in the researches of CTA. The medical fields directly related to face transplantation are microsurgery, immunology, and transplantation. Nowadays, each field is performed widely. Therefore people, even medical teams think face transplantation could be easily realized, sooner or later. But there are lots of things that should be prepared for not only practice and immunosuppression therapy but also for the cooperation with relevant fields. That's the reason why only 21 cases of face transplantation have been done, while more than 70 cases of hand transplantation have been done in the past years. Especially in Korea, brain death patients are not enough even for organ transplantation and furthermore there are some troubles in taking part in the society of transplantation. Face transplantation has lots of problems concerning variable medical fields, administration, society, ethics, and laws. Therefore, for the realization of face transplantation in Korea, not only medical skills but also political powers are needed.