• Journal of Microbiology and Biotechnology
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• v.26 no.6
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• pp.1035-1045
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• 2016

To evaluate the effects of lactic acid bacteria (LAB) on Peyer's patch cells, mice were treated with a high dose of kanamycin to disturb the gut microbial environment. The overarching goal was to explore the potential of LAB for use as a dietary probiotic that buffers the negative consequences of antibiotic treatment. In vitro, LAB stimulated the production of immunoglobulin A (IgA) from isolated Peyer's patch cells. Inflammation-related genes (TNF-α, IL-1β, and IL-8) were up-regulated in Caco-2 cells stimulated with lipopolysaccharide (LPS), while tight-junction-related genes (ZO-1 and occludin) were down-regulated; the effects of LPS on inflammatory gene and tight-junction gene expression were reversed by treatment with LAB. Mice treated with a high dose of kanamycin showed increased serum IgE levels and decreases in serum IgA and fecal IgA levels; the number of Peyer's patch cells decreased with kanamycin treatment. However, subsequent LAB treatment was effective in reducing the serum IgE level and recovering the serum IgA and fecal IgA levels, as well as the number of Peyer's patch cells. In addition, ZO-1 and occludin mRNA levels were up-regulated in the ileum tissues of mice receiving LAB treatment. Lactic acid bacteria can enhance the intestinal immune system by improving the integrity of the intestinal barrier and increasing the production of IgA in Peyer's patches. Lactic acid bacteria should be considered a potential probiotic candidate for improving intestinal immunity, particularly in mitigating the negative consequences of antibiotic use.

• Mycobiology
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• v.45 no.4
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• pp.297-311
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• 2017

Saprolegniasis is one of the most devastating oomycete diseases in freshwater fish which is caused by species in the genus Saprolegnia including Saprolegnia parasitica. In this study, we isolated the strain of S. parasitica from diseased rainbow trout in Korea. Morphological and molecular based identification confirmed that isolated oomycete belongs to the member of S. parasitica, supported by its typical features including cotton-like mycelium, zoospores and phylogenetic analysis with internal transcribed spacer region. Pathogenicity of isolated S. parasitica was developed in embryo, juvenile, and adult zebrafish as a disease model. Host-pathogen interaction in adult zebrafish was investigated at transcriptional level. Upon infection with S. parasitica, pathogen/antigen recognition and signaling (TLR2, TLR4b, TLR5b, NOD1, and major histocompatibility complex class I), pro/anti-inflammatory cytokines (interleukin $[IL]-1{\beta}$, tumor necrosis factor ${\alpha}$, IL-6, IL-8, interferon ${\gamma}$, IL-12, and IL-10), matrix metalloproteinase (MMP9 and MMP13), cell surface molecules ($CD8^+$ and $CD4^+$) and antioxidant enzymes (superoxide dismutase, catalase) related genes were differentially modulated at 3- and 12-hr post infection. As an anti-Saprolegnia agent, plant based lawsone was applied to investigate on the susceptibility of S. parasitica showing the minimum inhibitory concentration and percentage inhibition of radial growth as $200{\mu}g/mL$ and 31.8%, respectively. Moreover, natural lawsone changed the membrane permeability of S. parasitica mycelium and caused irreversible damage and disintegration to the cellular membranes of S. parasitica. Transcriptional responses of the genes of S. parasitica mycelium exposed to lawsone were altered, indicating that lawsone could be a potential anti-S. parasitica agent for controlling S. parasitica infection.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.5
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• pp.1337-1345
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• 2006

Hypercholesterolemia is a pivotal pathogenic factor for the development and maintenance of atherosclerosis. The present study was designed to evaluate whether the methanol extract of Sorbus commixta cortex (MSC) restores vascular dysfunction in association with the aortic expressions of proinflarnmatory and adhesion molecules in high cholesterol (HC) diet-rats. Chronic treatment with low (100 mg/kg/day) or high doses (200 mg/kg/day) of MSC lowered the increase in plasma levels of triglyceride (TG) and low-density lipoprotein (LDL) cholesterol induced by a cholesterol-enriched diet without affecting on the plasma level of high density lipoprotein (HDL)-cholesterol. Vascular tone attenuated in the HC-diet rats was restored by administration with MSC. Treatment with MSC also suppressed the HC-induced increase in the monocyte chemoattractant protein-1 (MCP-1) and nuclear factor-$_K$B (NF-$_K$B) p65 expressions as well as expressions levels of adhesion molecules including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (ICAM-1), and E-selectin in aorta. The present study also showed that MSC inhibited the HC-mediated induction of ET-1 and ACE expression. In histopathological examination, aortic segments in the HC-diet rat revealed thickening intima and media, which were blocked by administration with MSC. Taken together, MSC could suppress the development of atherosclerosis in the HC-diet rat model through the inhibition of the aortic expression levels of pro-inflammatory and adhesion molecules.

• Journal of Society of Preventive Korean Medicine
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• v.15 no.1
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• pp.49-69
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• 2011

Objective : The object of this study was to observe the effects of Lonicerae Flos (LF) aqueous extracts on lipopolysaccharide (LPS)-induced rat acute lung injury. Method : Five different dosages of LF extracts were orally administered once a day for 28 days before LPS treatments, and then all rats were sacrificed after 5 hour-treatment of LPS. Eight groups of 16 rats each were used in the present study. The following parameters caused by LPS treatment were observed ; body weights, lung weights, pulmonary transcapillary albumin transit, arterial gas parameters (pH, $PaO_2$ and $PaCO_2$) bronchoalveolar lavage fluid (BALF) protein lactate dehydrogenase (LDH), and proinflammatory cytokines tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$) contents, total cell numbers, neutrophil and alveolar macrophage ratios, lung malondialdehyde (MDA), myeloperoxidase (MPO), proinflammatory cytokines TNF-${\alpha}$ and IL-$1{\beta}$ contents. In addition, the histopathologic changes were observed in the lung in terms of luminal surface of alveolus, thickness of alveolar septum, number of polymorphonuclear neutrophils. Result : As results of LPS-injection, dramatical increases in lung weights, pulmonary transcapillary albumin transit increases, increases in $PaCO_2$, decreases in pH of arterial blood and $PaO_2$, increases of BALF protein, LDH, TNF-${\alpha}$ and IL-$1{\beta}$ contents, total cells, neutrophil and alveolar macrophage ratios, TNF-${\alpha}$ and IL-$1{\beta}$ contents increases were detected with decreases in LSA and increases of alveolar septum and PMNs numbers, respectively as compared with intact control. These are means that acute lung injuries (resembling acute respiratory distress syndrome) are induced by treatment of LPS mediated by inflammatory responses, oxidative stress and related lipid peroxidation in the present study. However, these LPS-induced acute lung injuries were inhibited by 28 days continuous pretreatment of 250 and 500mg/kg of LF extracts. Because of lower three dosages of LF treated groups, 31.25 and 62.5 and 125mg/kg did not showed any favorable effects as compared with LPS control, the effective dosages of LF in LPS-induced acute lung injuries in the present study, is considered as about 125mg/kg. The effects of 250mg/kg of LF extracts showed almost similar effects with ${\alpha}$-lipoic acid 60mg/kg in preventing LPS-induced acute lung injuries. Conclusion : It seems that LF play a role in protecting the acute respiratory distress syndrome caused by LPS.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.3
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• pp.700-704
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• 2007

In the recent, increased concern has been focused on the pharmacology and clinical utility of herbal extracts and derivatives as a drug or adjunct to chemotherapy and immunotherapy. Here we investigated the role of the extract of Anethi Fructus in the expression of inflammatory mediators, surface molecule, and related receptors in vitro. In murine macrophage RAW 264.7 cells and peritoneal macrophages of C57BL/6N mice, water extract of Anethi Fructus increased the production of secretary tumor necrosis factor (TNF)-a and Nitric oxide (NO), and the expression level of CD14, LPS co-receptor and CD86, co-stimulatory molecule compared to negative natural extract ex vivo. The water extract of Anethi Fructus increased the production of interferon (IFN)-g from splenocytes. Also, water extract of Anethi Fructus increased ConA-induced cell proliferation. These results suggest that water extract of Anethi Fructus may enhance the immune response through immune modulation of macrophage and lymphocytes.

• Biomolecules & Therapeutics
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• v.4 no.2
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• pp.127-137
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• 1996

This study was performed to investigate the toxicity of DA-125 in beagle dogs, an anthracycline antitumor antibiotic. The dogs were administered DA-125 i.v. at 0.0023, 0.0375, 0.15 and 0.6 mg/kg/day, 6 days/week for 26 weeks. At 0.6 mg/kg, all male and female dogs were either sacrificed moribundly or dead during the 26-week treatment. The dogs revealed inactivity, salivation, dark bloody discharge, swelling of the subcutaneous injection site, abscess, and ulceration in the abdominal wall and legs. At 0.15 mg/kg, anorexia, salivation, and swelling of the injection site were observed. The food consumption was decreased with a statistical significance at 6 and 12 weeks treatment in males of 7.6 mg/kg. At 0.0375, 0.15 and 0.6 mg/kg, body weights were decreased significantly in a dose-related fashion after 17 weeks treatment. Total white blood cell counts for male dogs at 0.6 mg/kg were lower than those of control dogs after 13 weeks treatment, which appeared mainly due to decreased neutrophils. At 0.15 mg/kg, testicular atrophy was found in all males by gross pathology and the testicular weights were significantly decreased when compared to those of control males. Microscopically, the testis showed moderate atrophy of the seminiferous tubules and marked decrease in number of spermatozoa in the epididymal tubules. At 0.6 mg/kg, petechia or echymotic hemorrhage was observed in gastrointestinal tract, heart, lungs, and other organs at the necropsy, Marked atrophy of thymus were observed in both males and females. In addition, severe testicular atrophy was noted in all males. Microscopically, gastrointestinal tract showed hemorrhage, epithelial denudation, hypermucus secretion, and atrophy of intestinal villi. Seminiferous tubules of the atrophic testis were lined with Sertoli cells only and devoid of germ cells. Severe oligospermia or aspermia was present in the epididymal tubules. Bone marrow showed marked depletion of hemopoietic cells. In addition, marked atrophy was found in the lymphoid tissue of gastrointestinal tract, various Iymph nodes, and thymus. Injection sites showed marked inflammatory response with necrosis, necrotizing vasculitis, thrombus formation, and ulceration in the skin. According to the present results, no observed effect level appeared to be 0.0375 mg/kg. At 0.15 mg/kg, testis was a target organ, while at 0.6 mg/kg hemopoietic tissue, gastrointestinal tract, and testis were considered to be target organs. At 0.6 mg/kg the test compound seems to inflict a damage on the blood vessels causing hemorrhage in the various organs and tissues.

• Biomolecules & Therapeutics
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• v.28 no.5
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• pp.456-464
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• 2020

Mast cells (MCs) are systemically distributed and secrete several allergic mediators such as histamine and leukotrienes to cause type I hypersensitivity. Dasatinib is a type of anti-cancer agent and it has also been reported to inhibit human basophils. However, dasatinib has not been reported for its inhibitory effects on MCs or type I hypersensitivity in mice. In this study, we examined the inhibitory effect of dasatinib on MCs and MC-mediated allergic response in vitro and in vivo. In vitro, dasatinib inhibited the degranulation of MCs by antigen stimulation in a dose-dependent manner (IC₅₀, ~34 nM for RBL-2H3 cells; ~52 nM for BMMCs) without any cytotoxicity. It also suppressed the secretion of inflammatory cytokines IL-4 and TNF-α by antigen stimulation. Furthermore, dasatinib inhibited MC-mediated passive cutaneous anaphylaxis (PCA) in mice (ED₅₀, ~29 mg/kg). Notably, dasatinib significantly suppressed the degranulation of MCs in the ear tissue. As the mechanism of its effect, dasatinib inhibited the activation of Syk and Syk-mediated downstream signaling proteins, LAT, PLCγ1, and three typical MAP kinases (Erk1/2, JNK, and p38), which are essential for the activation of MCs. Interestingly, in vitro tyrosine kinase assay, dasatinib directly inhibited the activities of Lyn and Fyn, the upstream tyrosine kinases of Syk in MCs. Taken together, dasatinib suppresses MCs and PCA in vitro and in vivo through the inhibition of Lyn and Fyn Src-family kinases. Therefore, we suggest the possibility of repositioning the anti-cancer drug dasatinib as a treatment for various MC-mediated type I hypersensitive diseases.

• Journal of Life Science
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• v.26 no.7
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• pp.789-795
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• 2016

A lymph node (LN) is one of the secondary lymphoid organs. An LN consists of a complicated 3 dimensional frame structure and several stromal cells. Fibroblastic reticular cells (FRC) are distributed in the T zone for interaction with T cells. FRC secrete homing chemokines such as CCL19 and CCL21. Moreover, FRC play a pivotal role in the production of extracellular matrix (ECM) into LN for ECM reorganization against pathogen infections. However, not much is known about the involvement of the immune reaction of FRC. The present report is for the characterization of FRC on immune response. For this, FRC were positioned in several infected situations such as co-culture with macrophage, lipopolysaccharide (LPS), and TNFα stimulation. When a co-culture between FRC and macrophage was performed, a morphological change in FRC was observed, and empty space between FRCs was created by this change. The soluble ICAM-1 protein level was up-regulated by co-culturing with Raw264.7 and the treatment of the ROCK inhibitor Y27632. The activity of matrix metalloproteinase (MMP) was up-regulated by LPS onto FRC. Furthermore, the inflammatory cytokine TNFα regulated the expression of ECM in FRC by a gene chip assay. Collectively, it suggests that FRC are involved in immune reactions.

• Journal of Life Science
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• v.17 no.3 s.83
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• pp.396-401
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• 2007

This research investigated whether exposure of diesel exhaust particulate (DEP) and particulate metter (PM) effect on intercellular. adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression in asthma-induced Balb/c and IL-10 knock out (KO) mouse. Mouse was sensitized with intraperitoneal injection with ovalbumin, followed by challenges with intranasal ovalbumin. After induction of asthma mouse placed in the inhalation chamber and exposed to DEP and PM (10 $mg/m^3$). The evidences of pulmonary inflammation were assessed by immunohistochemical stain and westen blot against ICAM-1 and VCAM-1 in the lung tissue. In the immunohistochemical stain, positive reactions for ICAM-1 and VCAM-1 were much stronger in asthma-induced groups and asthma-induced group with DEP or PM than control groups. Although mild positive reactions were appeared in asthma-induced IL-10 KO mice groups, positive reactions were very strong in the asthma-induced group with DEP or PM. In Western blot, expression of VCAM-1 was increased in asthma-induced group with DEP or PM than asthma-induced groups. In the IL-10 KO mouse, ICAM-1 and VCAM-1 expression were increased in asthma-induced group with DEP or PM than asthma-induced groups. DEP and PM exposure have additive effects on the aggravation of inflammatory signs in the asthma-induced murine model. These results suggest that inhalation of DEP and PM in asthmatic patients may aggravate clinical symptoms.

• The Korean Journal of Food And Nutrition
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• v.28 no.2
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• pp.253-257
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• 2015

Acanthopanax senticosus is an herb that has been used as a traditional remedy and medicine source. Its anti-inflammatory and, anti-oxidative effects have been reported in previous studies. This study aimed to investigate the effect of Acanthopanax senticosus water extracts on mouse macrophage cell in vitro. Mouse splenocyte proliferation increased after application of Acanthopanax senticosus water extract supplement of 5, 10, 50, 100, 250, 500, $1,000{\mu}g/mL$ after 48 h pre-treatment with a mitogen (ConA or LPS). The production of cytokines secreted by LPS and non LPS stimulated macrophages was detected by ELISA assay using a cytokine kit. Cytokine production (IL-2, IFN-${\gamma}$, and TNF-${\alpha}$) increased after water extract supplementation. The result of this in vitro study, showed that splenocyte proliferation and cytokine production by activated peritoneal macrophages were increased after Acanthopanax senticosus water extract in the range of $500{\sim}1,000{\mu}L/mL$. Thus, it is suggested that supplementation with Acanthopanax senticosus water extracts may enhance immune function by regulating splenocyte proliferation and enhancing cytokine production by activated macrophage.