• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.481-491
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• 2018

Allergic asthma is one of the most enduring diseases of the airway. The T-helper cells and regulatory T-cells are critically involved in inflammatory responses, mucus hypersecretion, airway remodelling and in airway hyper-responsiveness. Cigarette smoke (CS) has been found to aggravate inflammatory responses in asthma. Though currently employed drugs are effective, associated side effects demand identification and development of novel drugs with negligible or no adverse effects. Rutin, plant-derived flavonoid has been found to possess antioxidant and anti-inflammatory effects. We investigated the ability of rutin to modulate T-cells and inhibit inflammation in experimentally-induced asthma in cigarette smoke exposed mice. Separate groups of neonatal mice were exposed to CS for 10 days from post-natal days 2 to 11. After 2 weeks, the mice were sensitized and challenged with ovalbumin (OVA). Treatment group were given rutin (37.5 or 75 mg/kg body weight) during OVA sensitization and challenge. Rutin treatment was found to significantly inhibit cellular infiltration in the airways and Th2 and Th17 cytokine levels as well. Flow cytometry revealed effectively raised $CD4^+CD25^+Fox3^+$ Treg cells and supressed Th17 cell population on rutin treatment. Airway hyper-responsiveness observed following CS and OVA challenge were inhibited by rutin. $NF-{\kappa}B$ and iNOS, chief regulators of inflammatory responses robustly activated by CS and OVA were down-regulated by rutin. Rutin also inhibited the expression of matrix metalloproteinase 9, thereby aiding in prevention of airway remodelling in asthma thereby revealing to be a potent candidate in asthma therapy.

• BMB Reports
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• v.51 no.5
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• pp.207-208
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• 2018

Chitinase-Like Proteins (CLPs) are an evolutionarily conserved protein which lose their enzymatic activity for degrading chitin macromolecules. Chitinase-3-like-1 (Chi3l1) is a type of CLP that is highly expressed in epithelial cells, macrophages, etc., and is known to have correlations with type 2 inflammation and cancer. Although the increased level of Chi3l1 in the blood was reported in various disease patients, the function of Chi3l1 in adaptive immunity has been totally unknown. Recently, we found that Chi3l1 is expressed in T cells and has a negative regulatory role in T-cell activation and proliferation. A genetic ablation study of Chi3l1 in T cells showed hyperresponsiveness to TcR stimulation, which increased proliferation and Th1 differentiation. A significant increase of $IFN{\gamma}$ signaling in Chi3l1-deficient T cells synergistically increased Th1 and CTL functions against melanoma cells in vitro and in vivo. In addition, targeted knockdown by Chi3l1 siRNA complexed with the cell-penetrating peptide dNP2, which showed decreased pulmonary melanoma metastasis with increased infiltration of Th1 and CTL in the lung. This study first suggests that Chi3l1 is a novel regulator of Th1/CTL responses and could be a target for treating cancer to increase tumor immunity.

• Parasites, Hosts and Diseases
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• v.51 no.5
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• pp.583-588
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• 2013

To determine alteration of immune responses during visceral larva migrans (VLM) caused by Toxascaris leonina at several time points, we experimentally infected mice with embryonated eggs of T. leonina and measured T-helper (Th) cell-related serial cytokine production after infection. At day 5 post infection (PI), most larvae were detected from the lungs, spleen, intestine, and muscle. Expression of thymic stromal lymphopoietin (TSLP) and CCL11 (eotaxin) showed a significant increase in most infected organs, except the intestine. However, expression of the CXCL1 (Gro-${\alpha}$) gene was most highly enhanced in the intestine at day 14 PI. Th1-related cytokine secretion of splenocytes showed increases at day 28 PI, and the level showed a decrease at day 42 PI. Th2-related cytokine secretion of splenocytes also showed an increase after infection; in particular, IL-5 level showed a significant increase at day 14 PI, and the level showed a decrease at day 28 PI. However, levels of Th17-related cytokines, IL-6 and IL-17A, showed gradual increases until day 42 PI. In conclusion, Th1, Th2, and Th17-related cytokine production might be important in immune responses against T. leonina VLM in experimental mice.

• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.175-184
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• 1999

Background: Bronchial asthma is characterized by chronic eosinophilic inflammatory airway disease associated with bronchial hyperresponsiveness and reversible airway obstruction. Bronchial inflammation in asthma may depend in part on the activation of T helper lymphocytes that elaborate proinflammatory cytokines. T helper (Th) lymphocytes can be divided into two categories; Th1 lymphocytes, which secrete IL-2, IL-12 and IFN-$\gamma$, and Th2 lymphocytes, which secrete IL-4, IL-5, IL-6 and IL-10. Th2 lymphocytes appear to induce allergic responses, whereas Th1 lymphocytes induce delayed-type hypersensitivity response. Some infections, such as tuberculosis, cultivate a Th1 immunological environment and inhibit Th2 lymphocytes function. The presence of such infections might inhibit Th2 immune responses and thus protect development of atopic diseases. Method: 15 patients with allergic bronchial asthma, 10 patients with intrinsic bronchial asthma, and 10 healthy volunteers were studied. The serum concentrations of IFN-$\gamma$, IL-12, IL-4, IL-5, and IL-10 were measured by ELISA method and tuberculin skin test was estimated in different groups. Results: The positive response rates of tuberculin test were 46.7% in patients with allergic asthma, 100% in patients with intrinsic asthma and 60% in normal controls. The positive response rates were significantly lower in patients with allergic asthma than those of in patients with intrinsic asthma (p<0.05). Degree of responses to tuberculin test were $12.0{\pm}9.6mm$ in patients with allergic asthma, $18.4{\pm}4.5mm$ in patients with intrinsic asthma and $10.9{\pm}8.8mm$ in normal controls. The degree of responses were significantly reduced in patients with allergic asthma than those of patients with intrinsic asthma (p<0.05). The serum levels of IL-5 in patients with allergic asthma were significantly higher than in patients with intrinsic asthma and normal controls (p<0.05), although it was insignificant. the serum levels of IL-4 and IL-10 in patients with allergic asthma were higher than that of intrinsic asthma and normal controls. The serum levels of IL-12 and IFN-$\gamma$ in patients with allergic asthma and intrinsic asthma were significantly lower than those in normal controls(p<0.05). The serum levels of total immunoglobulin E (IgE) and peripheral blood eosinophile counts in patients with allergic asthma were significantly higher than those in normal controls. Peripheral blood esinophil counts had a significant correlation with the serum levels of total IgE, IL-5 and IL-10 in patients with allergic asthma (p<0.05). Conclusion: These results have showed that Th1 lymphocyte functions were lowered and Th2 lymphocyte functions were elevated in patients with allergic asthma than those in normal controls. Suppression of Th1 lymphocyte functions by activation of Th2 lymphocyte might be one of the important aspects of pathogenesis in allergic bronchial asthma.

• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.611-618
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• 2023

Rhizome of Alisma orientale has been used as a traditional medicine for treating kidney diseases in East Asian countries. Its inhibitory effects on hypersensitivity responses have been reported for methanol extracts, with alisol B 23-acetate (AB23Ac) being the most active constituent among six terpenes in inhibiting the direct passive Arthus reaction. However, whether AB23Ac has efficacy against allergic asthma has not been tested to date. The in vivo efficacy of AB23Ac in an ovalbumin (OVA)-induced allergic asthma mouse model was evaluated by administrating AB23Ac before OVA sensitization or OVA challenge in BALB/c mice. AB23Ac suppressed antigen-induced degranulation of RBL-2H3 mast cells in a concentration-dependent manner. The administration of AB23Ac both before OVA sensitization and OVA challenge greatly lowered pulmonary resistance and the increase in immune cell counts and inflammatory responses around the peribronchial and perivascular regions. In addition, the inflammatory cytokine levels of Th1/Th2/Th17 cells in the bronchoalveolar lavage fluid decreased in the AB23Ac-treated groups. AB23Ac reduced the number of PAS-stained cells in the lungs. Furthermore, a computer modeling study indicated that AB23Ac can bind tightly to spleen tyrosine kinase (Syk). These results suggest that AB23Ac may ameliorate allergic asthma by suppressing immune responses in dendritic cells during sensitization and in mast cells during challenge periods.

• Parasites, Hosts and Diseases
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• v.34 no.3
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• pp.185-190
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• 1996

The TH cytokine responses of spleen cells stimulated with Con A from mice infected with Polasonimw westemcni were examined. The spleen cell culture supema- tants were assayed for TH1-specific $IFN-{\gamma}$ and TH2-specific IL-4. Cytokine responses for IL-4 peaked at three days ($410{\;}{\pm}{\;}60.9{\;}pg/ml$), persisted at a high level until the second week ($343{\;}{\pm}{\;}59.0{\;}pg/ml$), and then decreased slowly four and six weeks after infection. $IFN-{\gamma}$ production by splenocytes only increased during the first week ($151{\;}{\pm}{\;}32.3{\;}pg/ml$) and declined abruptly after the second week of infection. IFN- y production by splenocytes of infected mice was not observed during the sixth week of infection. In addition, serum IL-4 and $IFN-{\gamma}$ were measured. Serum IL-4 was not detected in substantial quantity until four to six weeks after infection. The time course of serum IL-4 was not correlated with that of IL-4 production by splenocytes. Serum $IFN-{\gamma}$ was undetectable during the entire course of infection. These results suggest that TH2 cytokine responses, rather than TH1, predominate in mice infected with P. westemcni.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.42 no.4
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• pp.466-472
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• 1997

Vegetable perilla, "Ipdlkkae 1"(Perilla frutescens var japonica Hara), was tested about the flowering and maturing responce in summer and winter. In summer season, it was researched about those responses according to the change of seeding date from May 15th to Oct. 15th at one month interval in the field. "Ipdlkkae 1" flowered Oct. 2nd under the day length of eleven hours and fourty-one minutes, compared with Sep. 6th (day length of twelve hours and fourty-three minutes) of "Yepsildlggae". And those responses showed that vegetable perilla was have to seeded before July 15th for two reason. The first is a unique response of perilla to day length. If perilla stay under short-day condition for some days, perilla will flower after four weeks. The second is a weather, especially frost and cold. In the test of latest seeding at Oct. 15th, the plants flowered more late than normal flowering period and they were not able to mature for frost of early winter. And this result showed that any other species, which has the characteristic of later flowering than that of "Ipdlkkae 1", could not able to mature in the field. In winter time, this species was tested about the same responses according to the change of short-day treatments. In the case of the test from May 1st (above fourteen hours day length), even if the test plants were stayed under short-day condition for more than 10 days, they were not able to mature, but flowerd. From the test of Apr. 15th, day length of thirteen hours, the plants were showed variable reaction to the short-day treatment. In this test, 11days for short-day treatment was a basic day to decide whether flowering was delayed or not. In the test from Apr. 1st, perilla seeds were able to harvest at least 5 days short-day treatment. In the final test from Mar. 15th, it had no need to take short-day treatment for harvesting of normal seeds, because the day length of that are twelve hours, which is an enough time to induce flowering and maturing, previously reported.

• Asian-Australasian Journal of Animal Sciences
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• v.16 no.4
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• pp.541-548
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• 2003

The Immunoglobulin $IgG_1$ and $IgG_2$ isotype immune responses of domestic ruminants and mice to Cowdria. ruminantium live infection or by immunization with inactivated organisms were determined by the enzyme linked immunosorbent assay and Western blotting. Immunization of goats with inactivated elementary bodies (IEBs) led to a predominant $IgG_1$ isotype response. This indicated that a Th2 response was induced. After challenge, the IgG isotype responses were mixed whereby both $IgG_1$ and $IgG_2$ antibodies were detected. Two goats that survived virulent challenge had a predominant $IgG_2$ isotype response. In cattle live infection by natur l challenge or experiment led to a predominant $IgG_1$ isotype response. Immunization of cattle with IEBs however led to mixed IgG responses characterized by similar $IgG_1$ and $IgG_2$ ratios. In the mouse live infection led to a predominant $IgG_2$ isotype response. This indicated the mouse developed a true Th1 type cell mediated immune response when inoculated with live organisms. Immunization with inactivated organisms on the other hand led to a dominant $IgG_1$ response. It is evident from this work that the immune responses of ruminants and mice to C. ruminantium are different and that using mice as the experimental model for immune responses to Cowdria ruminantium. is not the appropriate.

• Nutrition Research and Practice
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• v.17 no.6
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• pp.1056-1069
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• 2023

BACKGROUND/OBJECTIVES: Grifola frondosa, commonly referred to as the maitake mushroom, has been studied extensively to explore its potential health benefits. However, its anti-inflammatory effects in skin disorders have not been sufficiently elucidated. This study aimed to elucidate the anti-inflammatory role of the ethanol extract of G. frondosa in atopic dermatitis (AD) using in vivo and in vitro models. MATERIALS/METHODS: We investigated its impact on skin and spleen inflammatory responses in Dermatophagoides farinae extract (DFE)/1-chloro-2,4 dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in a mouse model. Additionally, we determined the immunosuppressive response and mechanism of G. frondosa by inducing atopic-like immune reactions in keratinocytes through tumor necrosis factor (TNF)-α/interferon (IFN)-γ stimulation. RESULTS: Our study revealed that G. frondosa ameliorates clinical symptoms in an AD-like mouse model. These effects contributed to the suppression of Th1, Th2, Th17, and Th22 immune responses in the skin and spleen, leading to protection against cutaneous inflammation. Furthermore, G. frondosa inhibited the production of antibodies immunoglobulin (Ig)E and IgG2a in the serum of AD mice. Importantly, the inhibitory effect of G. frondosa on inflammatory cytokines in TNF-α/IFN-γ-stimulated AD-like keratinocytes was associated with the suppression of MAPK (Mitogen Activated Protein Kinase) pathway activation. CONCLUSIONS: Collectively, these findings highlight the potential of G. frondosa as a novel therapeutic agent for AD treatment and prevention.

• Journal of Microbiology and Biotechnology
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• v.26 no.6
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• pp.1132-1139
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• 2016

Brucellosis is a zoonotic disease caused by Brucella, a genus of gram-negative bacteria. Cytokines have key roles in the activation of innate and acquired immunities. Despite several research attempts to reveal the immune responses, the mechanism of Brucella infection remains unclear. Therefore, immune responses were analyzed in mice immunized with nine recombinant proteins. Cytokine production profiles were analyzed in the RAW 264.7 cells and naive splenocytes after stimulation with three recombinant proteins, metal-dependent hydrolase (r0628), bacterioferritin (rBfr), and thiamine transporter substrate-binding protein (rTbpA). Immune responses were analyzed by ELISA and ELISpot assay after immunization with proteins in mice. The production levels of NO, TNF-α, and IL-6 were time-dependently increased after having been stimulated with proteins in the RAW 264.7 cells. In naive splenocytes, the production of IFN-γ and IL-2 was increased after stimulation with the proteins. It was concluded that two recombinant proteins, r0628 and rTbpA, showed strong immunogenicity that was induced with Th1-related cytokines IFN-γ, IL-2, and TNF-α more than Th2-related cytokines IL-6, IL-4, and IL-5 in vitro. Conversely, a humoral immune response was activated by increasing the number of antigen-secreting cells specifically. Furthermore, these could be candidate diagnosis antigens for better understanding of brucellosis.