• The Korean Journal of Physiology and Pharmacology
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• v.2 no.1
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• pp.101-108
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• 1998

We investigated the effect of ${\alpha}-subunit$ of the stimulatory GTP-binding protein ($G{\alpha}_s$) gene mutation on the expression of the thyrotropin-releasing hormone (TRH) receptor (TRH-R) gene in GH3 cells and in growth hormone (GH)-secreting adenomas of acromegalic patients. In the presence of cyclohexicmide, forskolin and isobutylmethylxanthine, cholera toxin, and GH-releasing hormone (GHRH) decreased rat TRH-R (rTRH-R) gene expression by about 39%, 43.7%, and 46.7%, respectively. Transient expression of a vector expressing mutant-type $G{\alpha}_s$ decreased the rTRH-R gene expression by about 50% at 24 h of transfection, whereas a wild-type $G{\alpha}_s$ expression vector did not. The transcript of human TRH-R (hTRH-R) gene was detected in 6 of 8 (75%) tumors. Three of them (50%) showed the paradoxical GH response to TRH and the other three patients did not show the response. The relative expression of hTRH-R mRNA in the tumors from patients with the paradoxical response of GH to TRH did not differ from that in the tumors from patients without the paradoxical response. Direct PCR sequencing of $G{\alpha}_s$ gene disclosed a mutant allele and a normal allele only at codon 201 in 4 of 8 tumors. The paradoxical response to TRH was observed in 2 of 4 patients without the mutation, and 2 of 4 patients with the mutation. The hTRH-R gene expression of pituitaty adenomsa did not differ between the tumors without the mutation and those with mutation. The present study suggests that the expression of TRH-R gene is not likely to be a main determinant for the paradoxical response of GH to TRH, and that $G{\alpha}_s$ mutation may suppress the gene expression of TRH-R in GH-secreting adenoma. However, a certain predisposing factor(s) may play an important role in determining the expression of TRH-R.

• Journal of Microbiology and Biotechnology
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• v.18 no.8
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• pp.1393-1400
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• 2008

Recent study has demonstrated an increasing prevalence of food allergy in Korean children. Specific probiotic bacteria may promote potentially anti-allergenic processes through induction of Th1-type immunity and enhance the regulatory lymphocyte. This study investigated whether orally administrated probiotics could suppress allergic responses in an ovalbumin (OVA)-induced allergy mouse model. Thus, female C3H/HeJ mice were orally sensitized with OVA and cholera toxin for 4 weeks. Lactobacillus acidophilus AD031, Bifidobacterium lactis AD011, and L. acidophilus AD031 plus B. lactis AD011 were fed to mice from 2 weeks before the sensitization. The OVA-induced mice that were not treated with probiotics had significantly increased serum levels of OVA-specific IgE and IgG1, and OVA-specific IgA in feces. However, the mice treated with probiotics suppressed production of the OVA-specific IgE, IgG1, and IgA. The level of IL-4 was significantly lower, and the levels of INF-$\gamma$ and IL-10 were significantly higher in the mice treated with probiotics than that in the non-treated mice. The groups treated with probiotics had decreased levels of degranulated mast cells, eosinophil granules, and tail scabs. These results indicate that L. acidophilus AD031 and B. lactis AD011 might be useful for the prevention of allergy.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.4
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• pp.413-423
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• 1997

The importance of the kidney in the development of hypertension was first demonstrated by Goldblatt and his colleagues more than fifty years ago. Many hormones and other regulatory factors have been proposed to play a major role in the development of hypertension. Among these factors angiotensia II (ANG II) is closely involved in renal hypertension development since it directly regulates $Na^+$ reabsorption in the renal proximal tubule. Thus the aim of the present study was to examine signaling pathways of low dose of ANC II on the $Na^+$ uptake of primary cultured rabbit renal proximal tubule cells (PTCs) in hormonally defined seum-free medium. The results were as follows: 1) $10^{-11}$ M ANG II has a significant stimulatory effect on growth as compared with control. Alkaline phosphatase exhibited significantly increased activity. However, leucine aminopeptidase and ${\gamma}-glutamyl$ transpeptidase activity were not significant as compared with control. In contrast to $10^{-11}$ M ANG II stimulated $Na^+$ uptake $(108.03{\pm}2.16% of that of control)$, $10^{-9}$ M ANG II inhibited ($92.42{\mu}2.23%$ of that of control). The stimulatory effect of ANG II on $Na^+$ uptake was amiloride-sensitive and inhibited by losartan (ANG II receptor subtype 1 antagonist) and not by PD123319 (ANG II receptor subtype 2 antagonist). 2) Pertussis toxin (PTX) alone inhibited $Na^+$ uptake by $85.52{\pm}3.52%$ of that of control. In addition, PTX pretreatment prevented the AMG II-induced stimulation of $Na^+$ uptake. 8-Bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP), forskolin, and isobutylmethylxanthine (IBMX) alone inhibited $Na^+$ uptake by $88.79{\pm}2.56,\;80.63{\pm}4.38,\;and\;84.47{\pm}4.74%$ of that of control, respectively, and prevented the ANG II-induced stimulation of $Na^+$ uptake. However, $10^{-11}$ M ANG II did not stimulate cAMP production. 3) The addition of 12-O-te-tradecanoylphorbol-13-acetate (TPA, 0.01 ng/ml) to the PTCs produced significant increase in $Na^+$ uptake ($114.43{\pm}4.05%$ of that of control). When ANG II and TPA were added together to the PTCs, there was no additive effect on $Na^+$ uptake. Staurosporine alone had no effect on $Na^+$ uptake, but led to a complete inhibition of ANG II- or TPA-induced stimulation of Na'uptake. ANG II treatment resulted in a $111.83{\mu}4.51%$ increase in total protein kinase C (PKC) activity. In conclusion, the PTX-sensitive PKC pathway is the main signaling cascade involved in the stimulatory effects of ANG II on $Na^+$ uptake in the PTCs.

• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.227-233
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• 2021

Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon and ubiquitous environmental toxin with known harmful effects to human health. Abnormal phenotypes of keratinocytes are closely associated with their exposure to B[a]P. Resorcinol is a component of argan oil with reported anticancer activities, but its mechanism of action and potential effect on B[a]P damage to the skin is unknown. In this study, we investigated the effects of resorcinol on B[a]P-induced abnormal keratinocyte biology and its mechanisms of action in human epidermal keratinocyte cell line HaCaT. Resorcinol suppressed aryl hydrocarbon receptor (AhR) activity as evidenced by the inhibition of B[a]P-induced xenobiotic response element (XRE)-reporter activation and cytochrome P450 1A1 (CYP1A1) expression. In addition, resorcinol attenuated B[a]P-induced nuclear translocation of AhR, and production of ROS and pro-inflammatory cytokines. We also found that resorcinol increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activity. Antioxidant response element (ARE)-reporter activity and expression of ARE-dependent genes NAD(P)H dehydrogenase [quinone] 1 (NQO1), heme oxygenase-1 (HO-1) were increased by resorcinol. Consistently, resorcinol treatment induced nuclear localization of Nrf2 as seen by Western analysis. Knockdown of Nrf2 attenuated the resorcinol effects on ARE signaling, but knockdown of AhR did not affect resorcinol activation of Nrf2. This suggests that activation of antioxidant activity by resorcinol is not mediated by AhR. These results indicate that resorcinol is protective against effects of B[a]P exposure. The mechanism of action of resorcinol is inhibition of AhR and activation of Nrf2-mediated antioxidant signaling. Our findings suggest that resorcinol may have potential as a protective agent against B[a]P-containing pollutants.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.24 no.3
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• pp.1-16
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• 2011

Objective : In the theory of Korean medicine, Scrophulariae Radix (SR) can clear away heat and cool the blood, nourish yin and promote the production of the body fluids, relieve toxin and benefit the throat. The present study was carried out to investigate effects of SR on allergic contact dermatitis (ACD) induced by 2,4-dinitrochlorobenzene (DNCB) in mice. Methods : In this experiment, effects of SR on clinical aspects on the skin, histopathological changes such as spongiosis, mast cell distribution, immune cell infiltration in tissue, spleen / body ratio and production levels of serum cytokines were investigated in vivo. In addition, effects on cell viability and release of b-hexosaminidase and histamine were also investigated in vitro. Results : SR treatment diminished erythema, desquamation and keratosis which were induced by repeated painting of DNCB. Spongiosis and edema were diminished by painting of SR in histopathological observation, infiltrations of mast cell and monocytes were also decreased in SR group. In addition, spleen / body ratio was lowered compared to ADC control group. Production level of IFN-${\gamma}$ in serum was decreased, but level of IL-4 did not affected by SR. Finally, more than 400 ${\mu}g/ml$ of SR treatment groups showed decreased cell viabilities in RBL-2H3 cells. Treatment with over 200 ${\mu}g/ml$ of SR decreased b-hexosaminidase release, and treatment with over 400 ${\mu}g/ml$ decreased histamine release in vitro. Conclusion : these data suggest that SR can decrease symptoms of ACD, then SR is useful to treat patient with ACD.

• Korean Journal of Clinical Laboratory Science
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• v.49 no.2
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• pp.141-149
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• 2017

To examine the cause of acute diarrheal disease in children and adolescents, 521 fecal samples underwent multiple-PCR for a period of two years, between March 2015 and February 20178, in the Jeju region of Korea. Based on the analysis of 179 positive samples, 102 samples were male (56.98%) and 77 were female (43.02%), and highest positive rates were shown in the age group of 3~4 years (51.96%) and 5~6 years (12.29%). When 209 cases (40.12%), including double infection were analyzed, there were 88 cases (16.89%) of norovirus-GII infection, 26 cases (4.99%) of Campylobacter spp. infection, 18 cases (3.45%) of rotavirus infection, 18 cases (3.45%) of Clostridium difficile Toxin B infection, 17 cases (3.26%) of adenovirus infection, 16 cases (3.07%) of Clostridium perfringens infection, 11 cases (2.11%) of astrovirus infection, 5 cases (0.96%) of Salmonella spp. infection, 3 cases (0.58%) of norovirus-GI, Yersinia spp. and Aeromonas spp. infections, and 1 case (0.19%) of verocytotoxin-producing E. coli infection. Based on a seasonal separation of early childhood, norovirus-GI and norovirus-GII mainly prevailed during the winter, when the temperature is low. Typical enteritis with an increased prevalence of rotavirus during the spring. Astrovirus prevailed between the months of April and October, when norovirus-GI, norovirus-GII, and rotavirus did not prevail. With increasing age, acute diarrheal disease was not only induced by a virus, but also by bacteria. Although a test for virus is an effective method when trying to identify the cause during early childhood by multiplex-PCR, it would be desirable to undergo tests for both virus and bacteria concurrently as age increases.

• Journal of Microbiology and Biotechnology
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• v.24 no.7
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• pp.905-913
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• 2014

Lj-RGD3, an RGD (Arg-Gly-Asp) toxin protein from the salivary gland of Lampetra japonica, exhibits antifungal activity against Candida albicans. Lj-RGD3 has three RGD motifs and shows homology to histidine-rich glycoprotein. We synthesised two mutant derivatives of Lj-RGD3: Lj-26, which lacks all three RGD motifs and contains no His residues; and Lj-112, which lacks only the three RGD motifs. We investigated the effects of the wild-type and mutated toxins on a gram-positive bacterium (Escherichia coli), a gram-negative bacterium (Staphylococcus aureus), and a fungus (C. albicans). rLj-RGD3 and its mutants exhibited antifungal but not antibacterial activity, as measured by a radial diffusion assay. The C. albicans inhibition zone induced by rLj-112 was larger than that induced by the other proteins, and its inhibitory effect on C. albicans was dose-dependent. In viable-count assays, the rLj-112 MIC was $7.7{\mu}M$, whereas the MIC of the positive control (ketoconazole) was $15{\mu}M$. Time-kill kinetics demonstrated that rLj-112 effectively killed C. albicans at $1{\times}$ and $2{\times}$ MIC within 12 and 6 h, respectively. Electron microscopy analysis showed that rLj-RGD3 and rLj-112 induced C. albicans lysis. Our results demonstrate a novel anticandidal activity for rLj-RGD3 and its mutant derivatives.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4809-4813
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• 2014

Endocrine-disrupting chemicals (EDCs) have been reported to interfere with estrogen signaling. Exposure to these chemicals decreases the immune response and causes a wide range of diseases in animals and humans. Recently, many studies showed that licorice (Glycyrrhiza glabra) root extract (LRE) commonly called "gamcho" in Korea exhibits antioxidative, chemoprotective, and detoxifying properties. This study aimed to investigate the mechanism of action of LRE and to determine if and how LRE can alleviate the toxicity of EDCs. LRE was prepared by vacuum evaporation and freeze-drying after homogenization of licorice root powder that was soaked in 80% ethanol for 72 h. We used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a representative EDC, which is known to induce tumors or cancers; MCF-7 breast cancer cells, used as a tumor model, were treated with TCDD and various concentrations of LRE (0, 50, 100, 200, $400{\mu}g/mL$) for 24, 48, and 72 h. As a result, TCDD stimulated MCF-7 cell proliferation, but LRE significantly inhibited TCDD-induced MCF-7 cell proliferation in a dose- and time-dependent manner. The expression of TCDD toxicity-related genes, i.e., aryl hydrocarbon receptor (AhR), AhR nuclear translocator, and cytochrome P450 1A1, was also down-regulated by LRE in a dose-dependent manner. Analysis of cell cycle distribution after treatment of MCF-7 cells with TCDD showed that LRE inhibited the proliferation of MCF-7 cells via G2/M phase arrest. Reverse transcription-polymerase chain reaction and Western blot analysis also revealed that LRE dose-dependently increased the expression of the tumor suppressor genes p53 and p27 and down-regulated the expression of cell cycle-related genes. These data suggest that LRE can mitigate the tumorigenic effects of TCDD in breast cancer cells by suppression of AhR expression and cell cycle arrest. Thus, LRE can be used as a potential toxicity-alleviating agent against EDC-mediated diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5117-5121
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• 2014

Endocrine-disrupting chemicals (EDCs) have been reported to interfere with estrogen signaling. Exposure to these chemicals decreases the immune response and causes a wide range of diseases in animals and humans. Recently, many studies showed that licorice (Glycyrrhiza glabra) root extract (LRE) commonly called "gamcho" in Korea exhibits antioxidative, chemoprotective, and detoxifying properties. This study aimed to investigate the mechanism of action of LRE and to determine if and how LRE can alleviate the toxicity of EDCs. LRE was prepared by vacuum evaporation and freeze-drying after homogenization of licorice root powder that was soaked in 80% ethanol for 72 h. We used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as an EDC, which is known to induce tumors or cancers; MCF-7 breast cancer cells were used as a tumorigenic model. These were treated with TCDD and various concentrations of LRE (0, 50, 100, 200, $400{\mu}g/mL$) for 24, 48, and 72 h. As a result, TCDD stimulated MCF-7 cell proliferation, but LRE significantly inhibited TCDD-induced MCF-7 cell proliferation in a dose- and time-dependent manner. Expression of TCDD toxicity-related genes, i.e., aryl hydrocarbon receptor (AhR), AhR nuclear translocator, and cytochrome P450 1A1, were subsequently down-regulated by LRE in a dose-dependent manner. Analysis of cell cycle distribution after treatment of MCF-7 cells with TCDD and various concentrations of LRE showed that LRE inhibited the proliferation of MCF-7 cells via G2/M phase arrest. Reverse transcription-polymerase chain reaction and Western blot analyses also revealed that LRE dose-dependently increased the expression of the tumor suppressor genes p53 and p27 and down-regulated the expression of cell cycle-related genes. These data suggest that LRE can mitigate the tumorigenic effects of TCDD in breast cancer cells by suppression of AhR expression and cell cycle arrest. Thus, LRE can be used as a potential toxicity-alleviating agent against EDC-mediated disease.

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.11
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• pp.1592-1597
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• 2013

Type of dietary direct-fed microbials (DFMs) or poultry litter could directly influence the composition of gut microbiota. Gut microbiota plays an important role in shaping the developing immune system and maintaining the homeostasis of the mature immune system in mammal and chickens. The present study was carried out to investigate the interaction among litter, DFMs and immunity in broiler chickens exposed to a field-simulated environment. Immune status of broiler chickens was assessed by serum antibodies against Eimeria spp. and Clostridium spp. and intestinal cytokine mRNA expression. The current experimental design had a $3{\times}2$ factorial arrangement of treatments with three types of litter, i.e., fresh litter or used litter that was obtained from a farm with no disease outbreak (used litter) or a farm with history of a gangrenous dermatitis outbreak (GD litter), and two dietary treatments with or without DFMs. It was found that either DFM addition or type of litter significantly affected anticoccidial antibody levels of broiler chickens at d 42. In general, dietary DFMs increased the anticoccidial antibodies in the fresh-litter raised chickens, but lowered the levels in the GD-litter raised chickens. Serum antibodies against Clostridium perfringens ${\alpha}$-toxin were significantly (p<0.05) higher in chickens raised on GD litter compared with those raised on fresh litter. Cytokine mRNA expression was significantly (p<0.05) altered by either the type of litter or DFMs. Of interest, dietary DFMs lowered interferon-${\gamma}$, interleukin 1beta, and CXCLi2 cytokine mRNA expression in chickens raised on fresh litter but increased them in GD-litter raised chickens. In conclusion, dietary DFMs modulate various immune parameters of broiler chickens, but the DFM-mediated effects were dependent upon the type of litter on which chickens were raised.