• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.492-497
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• 2021

Levels of sphingosine 1-phosphate (S1P), an intercellular signaling molecule, reportedly increase in the bronchoalveolar lavage fluids of patients with asthma. Although the type 4 S1P receptor, S1P₄ has been detected in mast cells, its functions have been poorly investigated in an allergic asthma model in vivo. S1P₄ functions were evaluated following treatment of CYM50358, a selective antagonist of S1P₄, in an ovalbumin-induced allergic asthma model, and antigen-induced degranulation of mast cells. CYM50358 inhibited antigen-induced degranulation in RBL-2H3 mast cells. Eosinophil accumulation and an increase of Th2 cytokine levels were measured in the bronchoalveolar lavage fluid and via the inflammation of the lungs in ovalbumin-induced allergic asthma mice. CYM50358 administration before ovalbumin sensitization and before the antigen challenge strongly inhibited the increase of eosinophils and lymphocytes in the bronchoalveolar lavage fluid. CYM50358 administration inhibited the increase of IL-4 cytokines and serum IgE levels. Histological studies revealed that CYM50358 reduced inflammatory scores and PAS (periodic acid-Schiff)-stained cells in the lungs. The pro-allergic functions of S1P₄ were elucidated using in vitro mast cells and in vivo ovalbumin-induced allergic asthma model experiments. These results suggest that S1P₄ antagonist CYM50358 may have therapeutic potential in the treatment of allergic asthma.

• Journal of Pharmacopuncture
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• v.5 no.1 s.8
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• pp.135-151
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• 2002

Objective: This study was eanied out to investigate the effects of Raphani Semen on immuno-response in the mouse model of allergic asthma. Methods: In this study, BALB/C mice were divided into 6 groups: Normal (Non-treated group), Control (Group with not treated after allergic sensitization and induction by ovalbumin), Treat I (Group with the oral administration of saline after allergic sensitization and induction by ovalbumin), Treat n (Allergic asthma group treated with acupuncture (BL 13)), Treat III (Allergic asthma group treated with the oral administration of Raphani Semen) and Treat lV (Allergic asthma group treated with the herbal-acupuncture of Raphani Semen (BL 13)). The effect on cytokine was assessed by measuring cytokine (lL-2, IL-4, IL-5, IL-10, IL-12, IFN-r) in bronchoalveoar lavage fluid(ELISA). ResuJts : The results obtained as follows: 1. The production of Interleukin-2 was decreased significantly in Treat I group, Treat n group and Treat IV group as compared with Control group. 2. The production of Interleukin-4 was decreased significantly in Treat I group, Treat II group and Treat IV group as compared with Control group. Among them. the production of Interleukin-4 was decreased remarkably in Treat IV group as compared with other groups. 3. The production of Interleukin-5 was decreased significantly in Treat I group and Treat IV group as compared with Control group. 4. The production of Interleukin-10 was decreased significantly in Treat I group and Treat III group as compared with Control group. 5. The production of Interleukin-12 was all decreased significantly in Treat I group, Treat n group, Treat m group and Treat IV group as compared with Control group. 6. The production of Intelferon- showed no significant changes in Treat I group, Treat n group. Treat m group and Treat Ⅳ group as compared with Control group. Conclusion: These results show that the production of Interleukin-4, 5 was decreased significantly in aJlergic asthma group treated with the herbal-acupuncture of Raph Semen (BL 13), It is known that inactivity of Th2 cell constrained the revelation and controlled hypersenstive action. As to this mechanism, it is suggested that the herbal-acupuncture of Raphani Semen(BL 13) constrained the revelation of allergic asthma.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.29 no.2
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• pp.65-81
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• 2016

Objectives : Haedoksamul-tang (HSTE), a water extract from a mixture of Phellodendri Cortex, Coptidis, Scutellariae Radix, Gardeniae Fructus, Angelica acutiloba Radix, Cnidii Rhizoma, Paeoniae Radix, Rehmanniae Radix, has been traditionally used for allergic skin diseases such as atopic dermatitis and contact dermatitis in oriental countries. However, little is known about the effects of aqueous extract of HSTE on trimellitic anhydride (TMA)-induced contact hypersensitivity (CHS) in a mouse model. Methods : In this study, we investigate the pharmacological effects of HSTE on TMA-induced CHS in Balb/c mice. Contact hypersensitivity was induced in mice by topically sensitizing and challenging with TMA in flank skin and ears during oral administration (for 17 days) and topical treatment (30 min before challenge) with HSTE. We examined the effects of HSTE on IgE and IgG1 levels, inflammatory parameters in ear tissues, CD4⁺/CD8⁺ ratio, cytokine and chemokine production in sera, tissues, and immune cells from TMA-sensitized mice.Results : Oral and topical administration with HSTE reduced, in a dose dependent manner, thickness and leukocyte infiltration of ear tissues and IgE levels in serum from mice sensitized with TMA. In addition, auricula lymph node cells isolated from TMA-sensitized mice significantly elevated the expression ratio of CD4⁺/CD8⁺ as well as increased the production of IL-4, IL-5, IL-13 and IFN-γ by ex vivo stimulation with antibodies against CD3 and CD28, and these inflammatory indexes, except for IFN-γ, were significantly suppressed by orally and topically administration of HSTE. Furthermore, stimulation of auricula lymph node cells from TMA-sensitized mice with antibodies against CD3 and CD28 increased the production of MCP-1/CCL2 and MIP-1α/CCL3, and these effects were inhibited in a dose-dependent manner in cells from mice treated with HSTE. Conclusions : These results suggest that HSTE can be used for treating contact hypersensitivity by inhibiting leukocyte infiltration as well as production of serum IgE and chemokine/Th2 cytokine in an animal model.

• IMMUNE NETWORK
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• v.13 no.4
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• pp.157-162
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• 2013

Application of vaccine materials through oral mucosal route confers great economical advantage in animal farming industry due to much less vaccination cost compared with that of injection-based vaccination. In particular, oral administration of recombinant protein antigen against foot-and- mouth disease virus (FMDV) is an ideal strategy because it is safe from FMDV transmission during vaccine production and can induce antigen-specific immune response in mucosal compartments, where FMDV infection has been initiated, which is hardly achievable through parenteral immunization. Given that effective delivery of vaccine materials into immune inductive sites is prerequisite for effective oral mucosal vaccination, M cell-targeting strategy is crucial in successful vaccination since M cells are main gateway for luminal antigen influx into mucosal lymphoid tissue. Here, we applied previously identified M cell-targeting ligand Co1 to VP1 of FMDV in order to test the possible oral mucosal vaccination against FMDV infection. M cell-targeting ligand Co1-conjugated VP1 interacted efficiently with M cells of Peyer's patch. In addition, oral administration of ligand-conjugated VP1 enhanced the induction of VP1-specific IgG and IgA responses in systemic and mucosal compartments, respectively, in comparison with those from oral administration of VP1 alone. In addition, the enhanced VP1-specific immune response was found to be due to antigen-specific Th2-type cytokine production. Collectively, it is suggested that the M cell-targeting strategy could be applied to develop efficient oral mucosal vaccine against FMDV infection.

• IMMUNE NETWORK
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• v.11 no.4
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• pp.203-209
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• 2011

Background: T cell immunoglobulin mucin containing molecule (TIM)-3 is expressed in differentiated Th1 cells and is involved in the suppression of the cytokine production by these cells. However, the regulation of the expression of other T cell genes by TIM-3 is unclear. Herein, we attempted to identify differentially expressed genes in cells abundantly expressing TIM-3 compared to cells with low expression of TIM-3. Methods: TIM-3 overexpressing cell clones were established by transfection of Jurkat T cells with TIM-3 expression vector. For screening of differentially expressed genes, gene fishing technology based on reverse transcription-polymerase chain reaction (RT-PCR) using an annealing control primer system was used. The selected candidate genes were validated by semi quantitative and real-time RT-PCR. Results: The transcription of TIMP-1, IFITM1, PAR3 and CCL1 was different between TIM-3 overexpressing cells and control cells. However, only CCL1 transcription was significantly different in cells transiently transfected with TIM3 expression vector compared with control cells. CCL1 transcription was increased in primary human $CD4^+$ T cells abundantly expressing TIM-3 but not in cells with low expression of TIM-3. Conclusion: CCL1 was identified as a differentially transcribed gene in TIM-3-expressing $CD4^+$ T cells.

• Journal of Microbiology and Biotechnology
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• v.33 no.4
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• pp.441-448
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• 2023

Brucellosis is a contagious zoonotic disease that infects millions of people annually with hundreds of millions more being exposed. It is caused by Brucella, a highly infectious bacterial species capable of infecting humans with an estimated dose of 10-100 organisms. Sirtuin 1 (SIRT1) has been reported to contribute to prevention of viral diseases as well as a chronic infection caused by Mycobacterium bovis. Here, we investigated the role of SIRT1 in the establishment of Brucella abortus infection in both in vitro and in vivo systems using the reported SIRT1 activators resveratrol (RES), piceatannol (PIC), and ginsenoside Rg3 (Rg3). In RAW264.7 cells, SIRT1 activators did not alter the adherence of Brucella or Salmonella Typhimurium. However, reduced uptake of Brucella was observed in cells treated with PIC and Rg3, and survival of Brucella within the cells was only observed to decrease in cells that were treated with Rg3, while PIC treatment reduced the intracellular survival of Salmonella. SIRT1 treatment in mice via oral route resulted in augmented Brucella resistance for PIC and Rg3, but not RES. PIC treatment favors Th2 immune response despite reduced serum pro-inflammatory cytokine production, while Rg3-treated mice displayed high IL-12 and IFN-γ serum production. Overall, our findings encourage further investigation into the complete mechanisms of action of the different SIRT1 activators used as well as their potential benefit as an effective alternative approach against intracellular and extracellular pathogens.

• Korean Journal of Food Science and Technology
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• v.40 no.5
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• pp.574-579
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• 2008

Propolis is the generic term for the resinous substance collected by honey bees from a variety of plant sources. In this study, we have assessed the immunomodulatory properties of propolis (P) and fermented-propolis (FP) in BALB/c mice. Mice were subjected to gavage once a day (for 14 days) with 50, 100, 200 mg/kg body weight P, FP, or vehicle. Lymphocytes were isolated from the spleen and mesenteric lymph nodes (MLN) and the immune cell proportions, proliferative activities, and cytokine production were evaluated. The P- and FP-administration induced similar, but differential, alterations in the percentage of immune cell populations and their biological functions, including cytokine production and NK cell cytotoxicity. The proportion of$ CD4^+$ and $CD8^+$ T cells in the spleen was increased slightly in the P- and FP-administered mice as compared to the vehicle-treated mice. In MLN, the percentage of $CD4^+$ T cells was increased significantly in the 200 mg/kg P-treated mice. The mice which were treated with P and FP evidenced significantly increased interferon-$\gamma$ and interleukin-4 production in concanavalin A-stimulated splenocytes, whereas the production of theses cytokines was not shown to be induced by P-treatment. In addition, NK cell activity was also increased dramatically by the administration of P and FP. Collectively, these findings showed that P and FP are wide-spectrum immunomodulators, which may modulate both innate and adaptive immune responses.

• The Korean Journal of Food And Nutrition
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• v.31 no.2
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• pp.236-241
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• 2018

Flammulina velutipes is an edible mushroom and contains a lot of fiber, vitamin $B_1$, $B_2$, niacin and folic acid. This study was conducted to explore the effects of the Flammulina velutipes mushroom on immune cells and immunity. Th1 cytokine productions as $IFN-{\gamma}$, $TNF-{\alpha}$, and IL-2 were measured in an activated macrophage by Flammulina velutipes water extract in seven concentrations (0, 5, 10, 50, 100, 250, 500, and $1,000{\mu}g/mL$). Also, the splenocyte proliferation index was measured at 48 hours after treatment of the Flammulina velutipes water extract in seven concentrations or mitogen, LPS and ConA. The $IFN-{\gamma}$ and $TNF-{\alpha}$ productions were increased by treatment of the Flammulina velutipes water extract. The $TNF-{\alpha}$ production was significantly higher in the $50{\sim}1,000{\mu}g/mL$ Flammulina velutipes water extract treated macrophages. The $IFN-{\gamma}$ production of macrophages treated with the Flammulina velutipes water extract increased significantly in all groups, and the highest $1000{\mu}g/mL$ concentration. The splenocyte proliferation index was enhanced when the $10{\sim}1,000{\mu}g/mL$ Flammulina velutipes water extracts were treated compared to the control. These primary results suggest that Flammulina velutipes may enhance the immune function by activation of the macrophage and spleen cell.

• YAKHAK HOEJI
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• v.46 no.4
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• pp.258-264
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• 2002

Zinc plays an important role in immunobiological responses, while excessive zinc attenuates immune functions in a dose-dependent manner. Zinc excess has been reported to increase levels of plasma prostaglandin E$_2$ (PGE$_2$), which is known to inhibit production of Th (helper T) 1-associated cytokines and to induce inflammatory responses. Thus, this study was investigated the effects of indomethacin, a potent inhibitor of PGE$_2$ synthesis, on the proinflammatory cytokine and lymphokine production in ICR mice exposed to excessive zinc. Indomethacin at doses of 5 mg/kg was administered i.p. 30 minutes before zinc chloride (Zn) 30 mg/kg orally daily for 10 days. Excessive Zn remarkedly increased tumor necrosis factor (TNF)-$\alpha$ and interleukin (IL)-1$\beta$ levels in both serum and splenic supernatants compared with those in controls, while indomethacin significantly reduced the excessive Zn-induced levels of IL-1$\beta$. In serum, excessive Zn significantly decreased the levels of IL-2 and interferon (IFN)-${\gamma}$ compared with those in controls, whereas indomethacin significantly enhanced the excessive Zn-decreased levels of IFN-${\gamma}$ but did not affect the Zn-decreased levels of serum IL-2. In splenic supernatants, All of excessive Zn, indomethacin, and combination of Zn and indomethacin significantly enhanced IL-2 levels compared with those in controls, but indomethacin didn't affect the Zn-induced production of IL-2. These data, therefore, suggest that indomethacin significantly attenuated the in vivo and ex vivo IL-1$\beta$ production increased by excessive zinc and remarkedly enhanced the in vivo excessive zinc-suppressed production of IFN-${\gamma}$ but not IL-2.

• Clinical and Experimental Pediatrics
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• v.53 no.4
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• pp.481-487
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• 2010

Purpose: Recently many studies show early exposure during childhood growth to endotoxin (lipopolysaccharides, LPS) and/or early exposure to allergens exhibit important role in development of allergy including bronchial asthma. The aim of this study was to evaluate the role of endotoxin and allergen exposure in early life via the airways in the pathogenesis of allergic airways inflammation and airway hyperresposiveness (AHR) in mouse model of asthma. Methods: Less than one week-old Balb/c mice was used. Groups of mice were received either a single intranasal instillation of sterile physiologic saline, 1% ovalbumin (OVA), LPS or $1.0{\mu}g$ LPS in 1% OVA. On 35th day, these animals were sensitized with 1% OVA for 10 consecutive days via the airways. Animals were challenged with ovalbumin for 3 days on 55th days, and airway inflammation, hyperresponsiveness, and cytokine expression were assessed. Measurements of airway function were obtained in unrestrained animals, using whole-body plethysmography. Airway responsiveness was expressed in terms of % enhanced pause (Penh) increase from baseline to aerosolized methacholine. Lung eosinophilia, serum OVA-IgE and bronchoalveolar lavage (BAL) fluid cytokine levels were also assessed. ANOVA was used to determine the levels of difference between all groups. Comparisons for all pairs were performed by Tukey-Kramer honest significant difference test; $P$ values for significance were set to 0.05. Results: Sensitized and challenged mice with OVA showed significant airway eosinophilia and heightened responsiveness to methacholine. Early life exposure of OVA and/or LPS via the airway prevented both development of AHR as well as bronchoalveolar lavage fluid eosinophilia. Exposure with OVA or LPS also resulted in suppression of interleukin (IL)-4, 5 production in BAL fluid and OVA specific IgE in blood. Conclusion: These results indicate that antigen and/or LPS exposure in the early life results in inhibition of allergic responses to OVA in this mouse model of astham. Our data show that early life exposure with OVA and/or LPS may have a protective role in the development of allergic airway inflammation and development of allergen-induced airway responses in mouse model of asthma.