Immunoregulatory Therapeutics Group in Brain Busan 21 Project

Busan, South Korea

Immunoregulatory Therapeutics Group in Brain Busan 21 Project

Busan, South Korea
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Moon Y.,Pusan National University | Moon Y.,Immunoregulatory Therapeutics Group in Brain Busan 21 Project
Pediatric Gastroenterology, Hepatology and Nutrition | Year: 2016

The gastrointestinal exposome represents the integration of all xenobiotic components and host-derived endogenous components affecting the host health, disease progression and ultimately clinical outcomes during the lifespan. The human gut microbiome as a dynamic exposome of commensalism continuously interacts with other exogenous exposome as well as host sentineling components including the immune and neuroendocrine circuit. The composition and diversity of the microbiome are established on the basis of the luminal environment (physical, chemical and biological exposome) and host surveillance at each part of the gastrointestinal lining. Whereas the chemical exposome derived from nutrients and other xenobiotics can influence the dynamics of microbiome community (the stability, diversity, or resilience), the microbiomes reciprocally alter the bioavailability and activities of the chemical exposome in the mucosa. In particular, xenobiotic metabolites by the gut microbial enzymes can be either beneficial or detrimental to the host health although xenobiotics can alter the composition and diversity of the gut microbiome. The integration of the mucosal crosstalk in the exposome determines the fate of microbiome community and host response to the etiologic factors of disease. Therefore, the network between microbiome and other mucosal exposome would provide new insights into the clinical intervention against the mucosal or systemic disorders via regulation of the gut-associated immunological, metabolic, or neuroendocrine system. © 2016 by The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition.

Yu H.S.,Pusan National University | Yu H.S.,Immunoregulatory Therapeutics Group in Brain Busan 21 Project | Park M.-K.,Pusan National University | Park M.-K.,Immunoregulatory Therapeutics Group in Brain Busan 21 Project | And 5 more authors.
Stem Cell Research and Therapy | Year: 2017

Background: In a previous study, we demonstrated that intravenous administration of adipose tissue stem cells (ASCs) could significantly reduce allergic symptoms and suppress eosinophilic inflammation. Methods: To evaluate the secretome of ASCs, we administrated culture supernatant of ASCs (ASC sup, which contains the ASC secretome) and uncultured fresh medium (con sup) into a mouse model of allergic airway inflammation. Subsequently we observed the mice for signs of inflammation and investigated Th1-, Th2-, and Treg-related cytokine levels as well as recruitment of Treg cells into the airway. Results: We found that ASC sup could ameliorate allergic airway inflammation in this model; the value of airway hyperresponsiveness, and the occurrence of inflammatory cell infiltration in the lung, as well as the number of eosinophils, and goblet cells in the lung epithelium were all significantly decreased by ASC sup treatment. In addition, ASC sup treatment significantly decreased the levels of IL-4, IL-5, and IL-13 in the bronchial alveolar lavage fluid and in culture medium of lung-draining lymph node cells of the animal model of acute asthma. We detected numerous CTLA-4 and Foxp3-expressing cells in the lung after ASC sup treatment. ASC sup was found to have a higher concentration of IL-10 and TGF-β compared to con sup. Conclusions: Stem cells have powerful potential for therapeutic functions in various diseases, but they also have many drawbacks. In this study, we found strong immunosuppressive ability of ASC sup in an allergic airway mouse model. It may be possible to use ASC sup for treatment of many immunological diseases in the near future. © 2017 The Author(s).

Park M.K.,Pusan National University | Park M.K.,Immunoregulatory Therapeutics Group in Brain Busan 21 Project | Cho M.K.,Pusan National University | Kang S.A.,Pusan National University | And 5 more authors.
PLoS ONE | Year: 2014

Acanthamoeba is a free-living amoeba commonly present in the environment and often found in human airway cavities. Acanthamoeba possesses strong proteases that can elicit allergic airway inflammation. To our knowledge, the aeroallergenicity of Acanthamoeba has not been reported. We repeatedly inoculated mice with Acanthamoeba trophozoites or excretory-secretory (ES) proteins intra-nasally and evaluated symptoms and airway immune responses. Acanthamoeba trophozoites or ES proteins elicited immune responses in mice that resembled allergic airway inflammation. ES proteins had strong protease activity and activated the expression of several chemokine genes (CCL11 , CCL17, CCL22, TSLP, and IL-25) in mouse lung epithelial cells. The serine protease inhibitor phenyl-methane-sulfonyl fluoride (PMSF) inhibited ES protein activity. ES proteins also stimulated dendritic cells and enhanced the differentiation of naive T cells into IL-4-secreting T cells. After repeated inoculation of the protease-activated receptor 2 knockout mouse with ES proteins, airway inflammation and Th2 immune responses were markedly reduced, but not to basal levels. Furthermore, asthma patients had higher Acanthamoeba -specific IgE titers than healthy controls and we found Acanthamoeba specific antigen from house dust in typical living room. Our findings suggest that Acanthamoeba elicits allergic airway symptoms in mice via a protease allergen. In addition, it is possible that Acanthamoeba may be one of the triggers human airway allergic disease. © 2014 Park et al.

Park H.-K.,Pusan National University | Park M.-K.,Pusan National University | Park M.-K.,Immunoregulatory Therapeutics Group in Brain Busan 21 Project | Kim K.U.,Pusan National University | And 8 more authors.
Allergy and Asthma Proceedings | Year: 2016

Background: Acanthamoeba and their proteins can elicit severe allergic airway inflammation in experimental mice. Objective: Although Acanthamoeba can induce severe allergic airway inflammation in mice, there is no allergenicity data for humans. Methods: We performed a skin-prick test on 65 patients with chronic cough by using 54 previously known allergens and Acanthamoeba excretory-secretory proteins and enzyme-linked immunosorbent assay on 34 patients to evaluate Acanthamoeba-specific serum immunoglobulin (Ig) levels. To detect a novel Acanthamoeba allergen, Western blot analysis was performed on serum from patients who reacted positively to Acanthamoeba or some pollen allergens. Results: After skin-prick testing, 29 patients (44.6%) showed positive reactions to one or more common aeroallergens. Acanthamoeba allergenicity was evaluated in 4 of 65 subjects (6.1%). An Acanthamoeba-positive reaction was closely related to several pollen allergens, especially willow tree, poplar, elm, oak, velvet grass, and cockroach. Average levels of Acanthamoeba-specific IgG subtypes in patient serum did not differ compared with healthy subjects; however, Acanthamoeba-specific IgE titers of patients were significantly higher than in healthy subjects. IgE antibodies of patients who tested positive in the skin-prick test reacted strongly to the 15 kDa excretory-secretory protein. Moreover, these antigens also reacted with those who tested positive in the skin-prick test to pollens. Conclusion: Taken together, our results indicated that some patients with allergy showed a positive response to the skin-prick test and that they also have high IgE serum levels. However, further experimental investigation is warranted because our preliminary findings indicated that Acanthamoeba might be a new allergen in humans. Copyright © 2016, OceanSide Publications, Inc.

Cho M.K.,Pusan National University | Park M.K.,Pusan National University | Park M.K.,Immunoregulatory therapeutics group in Brain Busan 21 project | Kang S.A.,Pusan National University | And 8 more authors.
Parasite Immunology | Year: 2015

In our previous studies, the recombinant type II macrophage migration inhibitory factor homologue (rAs-MIF) secreted from Anisakis simplex suppressed experimental inflammation mouse model through IL-10 production and CD4+CD25+Foxp3+ T-cell recruitment. Also, TLR2 gene expression was significantly increased following rAs-MIF treatment. To know the relation between TLR2 and amelioration mechanisms of rAs-MIF, we induced allergic airway inflammation by ovalbumin and alum with or without rAs-MIF under TLR2 blocking systems [anti-TLR2-specific antibody (α-mTLR2 Ab) treatment and using TLR2 knockout mice]. As a result, the amelioration effects of rAs-MIF in allergic airway inflammation model (diminished inflammation and Th2 response in the lung, increased IL-10 secretion, CD4+CD25+Foxp3+ T-cell recruitment) were diminished under two of the TLR2 blocking model. The expression of TLR2 on the surface of lung epithelial cell was significantly elevated by rAs-MIF treatment or Pam3CSK (TLR2-specific agonist) treatment, but they might have some competition effect on the elevation of TLR2 expression. In addition, the elevation of IL-10 gene expression by rAs-MIF treatment was significantly inhibited by α-mTLR2 Ab or Pam3CSK pretreatment. In conclusion, anti-inflammatory effects of the rAs-MIF on OVA-induced allergic airway inflammation might be closely related to TLR2. © 2015 John Wiley & Sons Ltd.

Kim D.-H.,Pusan National University | Yu H.S.,Pusan National University | Yu H.S.,Immunoregulatory Therapeutics Group in Brain Busan 21 Project
PLoS ONE | Year: 2014

Although health education has proven to be cost-effective in slowing the spread of enterobiasis, assessments of the effectiveness of health education to reduce infectious diseases specifically in children are rare. To evaluate the effect of health education on knowledge, preventative practices, and the prevalence of enterobiasis, 319 children from 16 classes were divided into experimental and control groups. Data were collected from May 2012 to March 2013. A 40-minute in-class talk was given once in the experimental group. There were significant differences over the time in the mean scores for children's knowledge of Enterobius vermicularis infection in the intervention group compared to the control group (p<0.001). After the educational session, the score for knowledge about E. vermicularis infection increased from 60.2±2.32 to 92.7±1.19 in the experimental group; this gain was partially lost 3 months later, decreasing to 83.6±1.77 (p<0.001). Children's enterobiasis infection prevention practice scores also increased, from 3.23±0.27 to 3.73±0.25, 1 week after the educational session, a gain that was partially lost at 3 months, decreasing to 3.46±0.36 (p<0.001). The overall E. vermicularis egg detection rate was 4.4%; the rates for each school ranged from 0% to 12.9% at screening. The infection rate at 3 months after the treatment sharply decreased from 12.3% to 0.8% in the experimental group, compared to a decrease from 8.5% to 3.7% in the control group during the same period. We recommend that health education on enterobiasis be provided to children to increase their knowledge about enterobiasis and improve prevention practices. © 2014 Kim, Yu.

Moon Y.,Pusan National University | Moon Y.,Immunoregulatory Therapeutics Group in Brain Busan 21 Project
Mediators of Inflammation | Year: 2014

Ribosomal inactivation damages 28S ribosomal RNA by interfering with its functioning during gene translation, leading to stress responses linked to a variety of inflammatory disease processes. Although the primary effect of ribosomal inactivation in cells is the functional inhibition of global protein synthesis, early responsive gene products including proinflammatory cytokines are exclusively induced by toxic stress in highly dividing tissues such as lymphoid tissue and epithelia. In the present study, ribosomal inactivation-related modulation of cytokine production was reviewed in leukocyte and epithelial pathogenesis models to characterize mechanistic evidence of ribosome-derived cytokine induction and its implications for potent therapeutic targets of mucosal and systemic inflammatory illness, particularly those triggered by organellar dysfunctions. © 2014 Yuseok Moon.

Kang S.A.,Pusan National University | Kang S.A.,Immunoregulatory therapeutics group in Brain Busan 21 project | Park M.-K.,Pusan National University | Park M.-K.,Immunoregulatory therapeutics group in Brain Busan 21 project | And 9 more authors.
PLoS Neglected Tropical Diseases | Year: 2014

The recruitment of CD4+CD25+Foxp3+T (Treg) cells is one of the most important mechanisms by which parasites down-regulate the immune system.We compared the effects of Treg cells from Trichinella spiralis-infected mice and uninfected mice on experimental allergic airway inflammation in order to understand the functions of parasite-induced Treg cells. After four weeks of T. spiralis infection, we isolated Foxp3-GFP-expressing cells from transgenic mice using a cell sorter. We injected CD4+Foxp3+ cells from T. spiralis-infected [Inf(+)Foxp3+] or uninfected [Inf(-)Foxp3+] mice into the tail veins of C57BL/6 mice before the induction of inflammation or during inflammation. Inflammation was induced by ovalbumin (OVA)-alum sensitization and OVA challenge. The concentrations of the Th2-related cytokines IL-4, IL-5, and IL-13 in the bronchial alveolar lavage fluid and the levels of OVA-specific IgE and IgG1 in the serum were lower in mice that received intravenous application of Inf(+)Foxp3+ cells [IV(inf):+(+) group] than in control mice. Some features of allergic airway inflammation were ameliorated by the intravenous application of Inf(-)Foxp3+ cells [IV(inf):+(-) group], but the effects were less distinct than those observed in the IV(inf):+(+) group. We found that Inf(+)Foxp3+ cells migrated to inflammation sites in the lung and expressed higher levels of Treg-cell homing receptors (CCR5 and CCR9) and activation markers (Klrg1, Capg, GARP, Gzmb, OX40) than did Inf(-)Foxp3+ cells.T. spiralis infection promotes the proliferation and functional activation of Treg cells. Parasite-induced Treg cells migrate to the inflammation site and suppress immune responses more effectively than non-parasite-induced Treg cells. The adoptive transfer of Inf(+)Foxp3+ cells is an effective method for the treatment and prevention of allergic airway diseases in mice and is a promising therapeutic approach for the treatment of allergic airway diseases. © 2014 Kang et al.

Lee G.-H.,California State University, Chico | Lee J.-E.,Pusan National University | Park M.-K.,Pusan National University | Park M.-K.,Immunoregulatory Therapeutics Group in Brain Busan 21 Project | And 2 more authors.
Cornea | Year: 2016

Purpose: To evaluate adhesion of Acanthamoeba trophozoites to different silicone hydrogel contact lens (SHCL) generations with and without multipurpose contact lens care solution (MPS) treatment. Methods: Acanthamoeba lugdunensis L3a trophozoites were inoculated onto discs trimmed from SHCLs: first generation, Air Optix (Lotrafilcon B) with a plasma surface treatment, second generation, Acuvue Oasys (Senofilcon A), which contains an internal wetting agent (Hydraclear), and third generation, Biofinity (Comfilcon A) with no surface treatment. After 18-hour inoculation, the number of adherent trophozoites on SHCLs was counted as thecontrol under phase contrast microscopy. The effects of the 3 different MPSs, Opti-Free Express, ReNu Fresh, and Biotrue, soaking SHCLs for 6 hours, on Acanthamoeba adhesion were analyzed. Scanning electron microscopic examination was performed for assessment of Acanthamoeba attached on the lens surface. Results: Acanthamoeba trophozoites showed greater adhesion to Air Optix than to Acuvue Oasys and Biofinity (P , 0.05). On Air Optix and Acuvue Oasys, the number of adherent Acanthamoeba was significantly reduced compared with the control after treatment with Opti-Free Express (P , 0.05), but not significantly reduced by treatment with ReNu Fresh and Biotrue (P . 0.05). Acanthamoeba did not adhere to Biofinity regardless of MPSs treatment. Attachment of the acanthopodia of Acanthamoeba on the curved ridge of the Air Optix lens surface was observed. Conclusions: Acanthamoeba showed greater affinity for the firstgeneration SHCL and seemed to be more attached on SHCLs with more ridges. MPS with myristamidopropyl dimethylamine reduced the adhesion rate. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Lee M.H.,Pusan National University | Kim D.-H.,Pusan National University | Yu H.S.,Pusan National University | Yu H.S.,Immunoregulatory Therapeutics Group in Brain Busan 21 Project
Evidence-based Complementary and Alternative Medicine | Year: 2013

This study was conducted to evaluate the effects of guided imagery on stress and fatigue in patients undergoing radioactive iodine therapy after thyroidectomy in Korea. Participants were 84 individuals (44 for experimental group and 40 for control group) with thyroid cancer. The experimental group listened to a guided imagery CD once a day for 4 weeks. Global Assessment of Recent Stress and Revised Piper Fatigue Scale were self-administered, and heart rate variability was measured at three time points; prior to intervention (T1), just before intervention (T2) and 1 week later after intervention (T3). Heart rate variability was consisted of Standard Deviation of all NN interval (SDNN), Total Power (TP), Low Frequency (LF), and High Frequency (HF). There were significant decreases in stress (F = 28.45, P<0.001) and fatigue (F = 26.17, P<0.001) over time in the experimental group compared to the control group. Heart rate variability changed over time in the experimental group relative to the control group; SDNN (F = 6.68, P = 0.002), TP (F = 5.29, P=0.006), LF (F = 4.58, P = 0.012), and HF (F = 3.71, P=0.026). From the results of this study guided imagery can be recommended as an effective intervention to thyroid cancer patients with stress and fatigue. © 2013 Mi Hye Lee et al.

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