Potassium $(K^+)$ channels are present in airway smooth muscle cells, and their activation results in hyperpolarization and relaxation. Because these effects may have therapeutic relevance to hypersensitivity and asthma, we examined the effect of a potassium channel activator, cromakalim (BRL 34915, CK) on the release of mediators from superfused tracheal and parenchymal strips after passive sensitization with $IgG_1$ antibody. Both tissues were superfused with CK $(2{\times}10^{-6}\;M)$ for 30 min and challenged with CK and antigen (Ox-HSA). Using monodispersed, partially purified, highly purified guinea pig lung mast cells, we also examined the effect of CK on mediator release from these cells after passive sensitization with $IgG_{1}$ antibody $({\alpha}-OA)$. Guinea pig lung mast cells were purified using enzyme digestion method, count current elutriation, and discontinuous Percoll density gradient. After CK pretreatment, passively sensitized mast cells were challenged with varying concentration of antigen (OA, immunological stimuli) or with varying concentration of calcium ionophore (CaI, non-immunological stimuli). Histamine (Hist) release was determined by spectrophotofluorometry, and leukotrienes (LT) by radioimmunoassy. CK pretreatment decreased Hist by 35% and LT release by 40% in the antigen-induced tracheal tissue after $IgG_1$ sensitization but did not decrease the contractile response. In the antigen-induced parenchymal tissue CK decreased Hist release by 25% but poorly decreased LT. Both immunologic and non-immunologic stimuli caused a dose-dependent release of Hist and LT from monodispersed, partially purified and highly purified lung mast cells. Verification of LT release was obtained by the use of 5-lipoxygenase inhibitor, A64077 (Zileuton). CK decreased Hist and LT release by 20% respectively in the OA-induced guinea pig lung mast cells after $IgG_1$ sensitization. The inhibitory effects of CK on the Hist and LT release in the Ox-HSA-induced airway smooth muscle tissues or in the OA-induced and CaI-induced mast cells after $IgG_1$ sensitization were completely blocked by TEA and GBC. These studies show that guinea pig lung mast cells seem to be an important contributor to LT release, and that CK (which has been known as an airway smooth muscle relaxant) can in part act to inhibit mediator release in the antigen-induced airway smooth muscle, and that CK may also act to inhibit mediator release in the OA-induced and CaI-induced highly purified mast cells. These results suggest that Hist and LT release evoked by mast cell activation might in part be associated with $K{^+}4 channel activity.
In recent years, adjuvants have received much attention because of the development of purified subunit and synthetic vaccines which are poor immunogens and require adjuvants to evoke the immune response. Therefore, immunologic adjuvants have been developed and testing for most of this century. During the last years much progress has been made on development, isolation and chemical synthesis of alternative adjuvants such as derivatives of muramyl dipeptide, monophosphoryl lipid A, liposomes, QS-21, MF-59 and immunostimulating complexes (ISCOMS). Biodegradable polymer microspheres are being evaluated for targeting antigens on mucosal surfaces and for controlled release of vaccines with an aim to reduce the number of doses required for primary immunization. The most common adjuvants for human use today are aluminum hydroxide and aluminum phosphate. Calcium phosphate and oil emulsions have been also used in human vaccination. The biggest issue with the use of adjuvants for human vaccines is the toxicity and adverse side effects of most of the adjuvant formulations. Other problems with the development of adjuvants include restricted adjuvanticity of certain formulations to a few antigens, use of aluminum adjuvants as reference adjuvant preparations under suboptimal conditions, non-availability of reliable animal models, use of non-standard assays and biological differences between animal models and humans leading to the failure of promising formulations to show adjuvanticity in clinical trials. The availability of hundreds of different adjuvants has prompted a need for identifying rational standards for selection of adjuvant formulations based on safety and sound immunological principles for human vaccines. The aim of the present review is to put the recent findings into a broader perspective to facilitate the application of these adjuvants in general and experimental vaccinology.
Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
/
v.23
no.2
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pp.93-98
/
2012
Botulinum toxins are the most potent toxins known to mankind. Botulinum toxin acts by blocking the cholinergic neuromuscular or the cholinergic autonomic innervation of exocrine glands and smooth muscles. Seven distinct antigenic botulinum toxins (A, B, C, D, E, F and G) produced by different strains of Clostridium botulinum have been described and only A and B type of botulinum toxins were clinically used. Toxins were consisted of a heavy chain with a molecular weight of 100 kD and a light chain with a molecular weight of 50 kD. Toxins are bound with an astounding selectivity to glycoprotein structures located on the cholinergic nerve terminal. Subsequently light chain of toxin is internalized and cleaves different proteins of the acetylcholine transport protein cascade transporting the acetylcholine vesicle from the intracellular space into the synaptic cleft. After a decade of therapeutic application of the toxin, no anaphylaxis or deaths have been reported and systemic adverse effects have not been reported so far. However the toxin's immunologic properties can lead to the stimulation of antibody production, potentially rendering further treatments ineffective. Botulinum toxin is a safe and effective treatment. Use of botulinum toxin in clinical medicine has grown exponentially in recent years, and many parts of the human body are now being targeted for therapeutic purposes.
Objective : Allergic disease, a very common chronic illness that affects all ages of patients, has been well characterized as an IgE-dependent immunologic response. Recently, interest has grown about the late inflammatory reaction as well as the early one characterized by IgE and mast cells in allergic disease. The purpose of this study was to find the anti-inflammatory effect of Taeeumjowui-tang (Taiyintiaowei-tang) in allergic reaction. Methods : The experiment was performed using Raw 264.7 cells pretreated with Taeeumjowui-tang contents extracts. The results were measured for different concentrations of Taeeumjowui-tang extracts (100, 200, $300{\mu}g$/ml): the toxicity and proliferation of cells by MTT analysis, LPS-induced NO production using Griess reagent and IL-6/ TNF-${\alpha}$ production, which is a significant criteria for diagnosing allergic reaction. Results : No toxicity of Taeeumjowui-tang (100, 200, $300{\mu}g$/ml) on Raw 264.7 cells was found after 24 hours incubation. LPS-induced NO production was reduced after treatment with Taeeumjowui-tang (100, 200, $300{\mu}g$/ml)(P<0.001). IL-6 decreased only at $100{\mu}g$/ml(P<0.05). TNF-${\alpha}$ production decreased only at $300{\mu}g$/ml, but still statistically insignificant. There was no relationship between any components of Taeeumjowui-tang alone and inhibition of NO production. Conclusions : These data suggest that Taeeumjowui-tang has anti-inflammatory effects in allergic reaction.
Kim, Kee Won;Park, Suk Young;Lee, Kyung Bock;Kim, Hyun-su
IMMUNE NETWORK
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v.4
no.2
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pp.88-93
/
2004
Background: Bone marrow mesenchymal stem cells (MSC) inhibit the immune response of lymphocytes to specific antigens and dendritic cells (DC) are professional antigenpresenting cells whose function is to present antigen to naive T-lymphocytes with high efficiency and play a central role in the regulation of immune response. We studied the effects of MSC on DC to evaluate the relationship between MSC and DC in transplantation immunology. Methods: MSC were expanded from the bone marrow and DC were cultured from peripheral blood mononuclear cells (PBMNC) of 6 myelogenous leukemia after achieving complete response. Responder cells isolated from PBMNC and lysates of autologous leukemic cells are used as tumor antigen. The effect of MSC on the DC was analyzed by immunophenotype properties of DC and by proliferative capacity and the amount of cytokine production with activated PBMNC against the allogeneic lymphocytes. Also, cytotoxicity tests against leukemic cells studied to evaluate the immunologic effect of MSC on the DC. Results: MSC inhibit the CD83 and HLA-class II molecules of antigen-loaded DC. The proliferative capacity and the amount of INF-$\gamma$ production of lymphocytes to allogeneic lymphocytes were decreased in DC co-cultured with MSC. Also the cytotoxic activity of lymphocytes against leukemic cells was decreased in DC co-cultured with MSC. Conclusion: MSC inhibit the activation and immune response of DC induced by allogeneic or tumor antigen.
Purpose: Eupatilin is an antioxidative flavone and a phytopharmaceutical derived from Artemisia asiatica. It has been reported to possess anti-tumor activity in some types of cancer including gastric cancer. Eupatilin may modulate the angiogenesis pathway which is part of anti-inflammatory effect demonstrated in gastric mucosal injury models. Here we investigated the anti-tumor effects of eupatilin on gastric cancer cells and elucidated the potential underlying mechanism whereby eupatilin suppresses angiogenesis and tumor growth. Materials and Methods: The impact of eupatilin on the expression of angiogenesis pathway proteins was assessed using western blots in MKN45 cells. Using a chromatin immunoprecipitation assay, we tested whether eupatilin affects the recruitment of signal transducer and activator of transcription 3 (STAT3), aryl hydrocarbon receptor nuclear translocator (ARNT) and hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) to the human VEGF promoter. To investigate the effect of eupatilin on vasculogenesis, tube formation assays were conducted using human umbilical vein endothelial cells (HUVECs). The effect of eupatilin on tumor suppression in mouse xenografts was assessed. Results: Eupatilin significantly reduced VEGF, ARNT and STAT3 expression prominently under hypoxic conditions. The recruitment of STAT3, ARNT and HIF-$1{\alpha}$ to the VEGF promoter was inhibited by eupatilin treatment. HUVECs produced much foreshortened and severely broken tubes with eupatilin treatment. In addition, eupatilin effectively reduced tumor growth in a mouse xenograft model. Conclusions: Our results indicate that eupatilin inhibits angiogenesis in gastric cancer cells by blocking STAT3 and VEGF expression, suggesting its therapeutic potential in the treatment of gastric cancer.
Gold therapy of rheumatoid arthritis is effective, but adverse reactions are also common. There are some cutaneous, hematologic, renal, and pulmonary side effects which have been associated with immunologic abnormalities. Also, hypersensitivity pneumonitis induced by gold therapy was rarely reported in literature. But, the mechanism for the induction of the pulmonary disease is not known. We report a case of seropositive rheumatoid arthritis presented as gold induced hypersensitivity pneumonitis which was confirmed by the peripheral blood lymphocyte stimulation test with gold.
Eun, Seok Chan;Kim, Byung Jun;Kim, Jin Hee;Heo, Chan Yeong;Baek, Rong Min;Chang, Hak;Minn, Kyung Won
Archives of Plastic Surgery
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v.35
no.4
/
pp.367-372
/
2008
Purpose: Prevention of acute rejection in skin allografts without continuous immunosuppression lacks reports in worldwide literature. Needs for chronic immunosuppression preclude the use of tissue allograft as a routine surgical reconstructive option. Recently dendritic cells(DC) gained considerable attention as antigen presenting cells that are also capable of immunologic tolerance induction. This study assesses the effects of alloantigen-pulsed dendritic cells in induction of survival increase in a rat skin allograft model. Methods: Recipient-derived dendritic cells were harvested from rat whole blood and cultured with GM-CSF(200 ng/mL) and IL-4(8 ng/mL) for 2 weeks. Then donor-specific alloantigen pulsed dendritic cells were reinjected into tail vein before skin graft. The rat dorsal skin allografts were transplanted in 5 subgroups. Groups: I) untreated, II) anti-lymphocyte serum(ALS, 0.5 mL), III) FK-506(2 mg/kg), IV) DCp, VI) DCp and FK-506. Graft appearance challenges were assessed postoperatively. Results: The group V(DC and FK-506 treated) showed longest graft survival rate(23.5 days) than other groups; untreated(5.8 days), ALS(7.2 days), FK-506 (17.5 days), DCp(12.2 days). Conclusion: Donor antigen pulsed host dendritic cell combined with short-term immunosuppression prolong skin allograft survival and has potential therapeutic application for induction of donor antigen specific tolerance.
Park, Young-Joo;Ryu, Ho-Sihn;Han, Keum-Sun;Kwon, Jung-Hye;Kim, Han-Kyeom;Cho, Yoon-Jung;Kang, Hyun-Cheol;Cheon, Suk-Hee;Yoon, Ji-Won
Journal of Korean Academy of Nursing
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v.39
no.1
/
pp.145-156
/
2009
Purpose: This study was done to develop a school-based anger management program (SAMP) of 4 sessions and examine its effects on the anger, anger expression, psychosomatic responses, psychosocial responses, and immunologic responses in adolescents. Methods: A quasi-experimental study using a nonequivalent control group, pre-post design with repeated measures was used. Chi-square test, t-test, paired t-test, and Fisher's exact test were used to analyze the data. Results: There were no differences between the experimental and control groups in outcome variables except for lymphocytes. However, following additional analyses, statistically significant differences by time point were observed for pain sensitivity, T cell, Helper T (Th) cell, Suppressor (Ts) cell and Natural Killer (NK) cell post-treatment, entrapment and psychosomatic symptoms at the 4-week follow-up, and resilience at the 10-week follow-up for the experimental group. Conclusion: Although some modifications in contents and administration will be required to increase the effectiveness of the program for anger management, SAMP can be used to promote anger management ability in adolescents.
Induction of effective and increased levels of antibody production may be major points in vaccine development. This is especially the case when the antigenic sources are carbohydrates. Thus, in our Lab various types of formulations such as liposomal and conjugate vaccines have been researched. However, the fastidious formulation process and high costs are a problem. For this reason, there is currently a focus on utilizing immunoadjuvants. In this present study, we tested whether ginsenosides Re (a panaxdiol) and Rg1 (a panaxtriol) from Panax ginseng have immunoadjuvant activity against the cell wall of Candida albicans (CACW). The resulting data showed that Rd and Rg1 caused LPS-treated B lymphocytes to be proliferative. Rd had greater proliferation activity than that of Rg1. In the murine model of antibody production, CACW combined with Rd [CACW/Rd/IFA] or Rg1 [CACW/Rg1/IFA] increased the production of antibodies specific to C. albicans when compared to the antibody production by [CACW/IFA]-induction, which was used as a negative control (P<0.05). In the case of [CFA/Rd/IFA], the antibody production was almost twice as that of the CFA. In addition, formulations containing either had a prolonged antibody inducing activity as compared to the CFA formula. In conclusion, Rd and Rg1 have an immunologic activity, and yet Rd can be a better candidate than Rg1 for a new immunoadjuvant.
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