• Archives of Pharmacal Research
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• v.19 no.5
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• pp.374-380
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• 1996

Sprague-Dawley male rats (150 g) were chronically treated with 5 v/v % ethanol admixed with nutritionally complete liquid diet and fed ad libitum for 3 weeks. One half of each group was exposed to cold stress at 4 ^{\circ}C either for 24 h (for determination of mRNA by in situ hybridization) or for 48 h (for determination of enzyme activity). Chronic ethanol treatment (ethanol) did not affect tyrosine hydroxylase(TH) mRNA level in locus coeruleus(LC) of brain and adrenal medulla(AM) compared to controls. Cold stress showed strong increase of TH mRNA level in LC and AM compared to controls. Pretreated ethanol reduced the increased TH mRNA level by cold stress in LC and AM. Ethanol did not affect TH activity in LC and adenal glands(adrenals). Cold stress increased TH activity in LC but not in adrenals. Pretreated ethanol did not reduce the increased TH activity by cold stress in LC but this result was not shown in adrenals. Phenylethanolamine-N-methyltransferase(PNMT) activity in $C_{1}$$C_{2}$ and adrenals increased only in ethanol treated group. THese results suggest that ethanol does not affect TH mRNA level and activity in LC and adrenals, but increases PNMT activity in $C_{1}$$C_{2}$ and adrenals in normal rat. It is also suggested that pretreated ethanol reduces the magnitude of cold stress response, that is induction of TH mRNA in LC and AM, and does not reduce the protein activation of TH that is also cold stress response in LC.

• Biomolecules & Therapeutics
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• v.17 no.4
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• pp.388-394
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• 2009

The cytokines which is produced by allergen-specific T helper (Th) cells play a pivotal role in the pathogenesis of asthma. Asthma is caused by exaggerated T-helper 2 (Th2)-based immune responses. It is suggested that controlling such Th2-based response is necessary for asthma therapy. The current therapies for asthma focus primarily on control of symptoms and suppression of inflammation, without affecting the underlying cause. So, we examined that anti-asthmatic drugs might have play a certain role in Th2/Th1 balance. Splenocytes isolated from ovalbumin (OVA)-sensitized mice cultured with anti-asthmatic drugs. It is well known that Th2 and Th1 immune responses can balance one another, as Th2 mediators suppress Th1 responses and Th1 mediators similarly inhibit Th2 responses. But salmeterol inhibits both of Th1 and Th2 mediators, which salmeterol is a suppressor of immune responses not only a suppressor of Th2-based immune responses. Aminophylline is a weak suppressor of immune responses. But ipratropium and cromoglycate don't have any suppressor effect to Th2-driven responses. They only have suppressor effect to Th1 immune responses. Salmeterol, ipratropium, aminophylline, and cromoglycate augmented mRNA levels of CRTH2, EP2, and IP2 receptors in OVA-sensitized splenocytes. It is well known that the up-regulation of CRTH2 - $PGD_2$ receptor - results in restraint of eosinophil recruitment and that the increment of IP and EP2 - $PGI_2$ and $PGE_2$ receptor, respectively - may induce the accumulation of cAMP that decrease the effector function of T cells. Moreover salmeterol and cromoglycate increase the mRNA expression of $PGD_2$ synthase. These findings indicate that anti-asthma agents may alleviate the immunological responses that cause the asthmatic diseases.

• IMMUNE NETWORK
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• v.23 no.2
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• pp.16.1-16.19
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• 2023

Bacillus Calmette-Guerin (BCG) vaccine is the only licensed vaccine for tuberculosis (TB) prevention. Previously, our group demonstrated the vaccine potential of Rv0351 and Rv3628 against Mycobacterium tuberculosis (Mtb) infection by directing Th1-biased CD4⁺ T cells co-expressing IFN-γ, TNF-α, and IL-2 in the lungs. Here, we assessed immunogenicity and vaccine potential of the combined Ags (Rv0351/Rv3628) formulated in different adjuvants as subunit booster in BCG-primed mice against hypervirulent clinical Mtb strain K (Mtb K). Compared to BCG-only or subunit-only vaccine, BCG prime and subunit boost regimen exhibited significantly enhanced Th1 response. Next, we evaluated the immunogenicity to the combined Ags when formulated with four different types of monophosphoryl lipid A (MPL)-based adjuvants: 1) dimethyldioctadecylammonium bromide (DDA), MPL, and trehalose dicorynomycolate (TDM) in liposome form (DMT), 2) MPL and Poly I:C in liposome form (MP), 3) MPL, Poly I:C, and QS21 in liposome form (MPQ), and 4) MPL and Poly I:C in squalene emulsion form (MPS). MPQ and MPS displayed greater adjuvancity in Th1 induction than DMT or MP did. Especially, BCG prime and subunit-MPS boost regimen significantly reduced the bacterial loads and pulmonary inflammation against Mtb K infection when compared to BCG-only vaccine at a chronic stage of TB disease. Collectively, our findings highlighted the importance of adjuvant components and formulation to induce the enhanced protection with an optimal Th1 response.

• YAKHAK HOEJI
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• v.56 no.6
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• pp.366-371
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• 2012

In this present study, we determined whether or not there is an immunoadjuvant effect of ochnaflavone, a biflavone isolated from Lonicera japonica. As an antigenic source, the cell wall (CACW) of Candida albicans, a fungal pathogen, was used. CACW consists of 95% carbohydrate (mannan). In the experiments, BALB/c mice were immunized with emersion forms of CACW combined with or without ochnaflavone (Och) in the presence of IFA containing mineral oil or CACW alone. Then, the amounts of antisera collected from these mice groups were measured by the ELISA method. Data from these experiments showed that CACW combined with Och (CACW/Och/IFA) provoked the production of antisera app. 2.2 or 5 times more than the corresponding CACW/IFA or CACW alone (CACW/DPBS), respectively, in mice (P<0.05). We further examined the immune response type induced by Och. Analysis of the values of the IgG1/IgG2a ratios obtained from IgG isotyping revealed that Och induced Th2-immunity more dominantly than Th1. This finding was confirmed by cytokine profile. CACW/Och/IFA formulation induced IL-4 (Th2-type cytokine) more than IFN${\gamma}$ (Th1-type cytokine) as compared with CACW/IFA and CACW/DPBS formulations (P<0.05). All data combined, Och appears to have an immunoadjuvant activity that may convert Th1 immunity into Th2 immunity.

• Journal of Microbiology and Biotechnology
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• v.26 no.3
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• pp.469-476
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• 2016

This study was undertaken to evaluate the immunomodulatory effect of dead nano-sized Lactobacillus plantarum (nLp) in RAW 264.7 cells and murine primary splenocytes. nLp is a dead, shrunken, processed form of L. plantarum nF1 isolated from kimchi (a traditional Korean fermented cabbage) and is less than 1 μm in size. It was found that nLp treatment stimulated nitric oxide (NO) production more in RAW 264.7 macrophages than pure live L. plantarum (pLp), and that the stimulatory properties were probably largely derived from its cell wall. In addition, nLp induced murine splenocyte proliferation more so than pLp; in particular, a high dose of nLp (1.0 × 10¹¹ CFU/ml) stimulated proliferation as much as lipopolysaccharide at 2 μg/ml. Moreover, according to our cytokine profile results in splenocytes, nLp treatment promoted Th1 (TNF-α, IL-12 p70) responses rather than Th2 (IL-4, IL-5) responses and also increased Th17 (IL-6, IL-17A) responses. Thus, nLp stimulated NO release in RAW 264.7 cells and induced splenocyte proliferation more so than pLp and stimulated Th1 and Th17 cytokine production. These findings suggested that dead nLp has potential use as a functional food ingredient to improve the immune response, and especially as a means of inducing Th1/Th17 immune responses.

• Clinical and Experimental Reproductive Medicine
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• v.37 no.3
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• pp.231-237
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• 2010

Objective: To evaluate whether T helper 1 (Th1) immune response is predominant in women with reproductive failures (recurrent spontaneous abortion and recurrent implantation failure) and the activation of T cell is related to Th1 propensity. Methods: Women with a history of recurrent implantation failure or recurrent spontaneous abortion comprise the study group (n=37). Controls are normal fertile women without a history of infertility or pregnancy losses (n=11). Th1/Th2 ratios of interferon (INF)-$\gamma$/interleukin (IL)-10 and tumor necrosis factor (TNF)-$\alpha$/IL-10 expression on $CD3^+/4^+$ cells, CD154, and CD69 expression on T cells are measured by flow cytometric analysis. Results: The ratios of TNF-$\alpha$ to IL-10 expressing on $CD3^+/4^+$ cells (Th1/Th2 cell ratios) are significantly higher in study group ($42.1{\pm}2.3$) as compared with that of controls ($28.7{\pm}2.7$) (p=0.002). The overall trend of CD154 and CD69 expression on T cells are elevated in study group than those of controls. The proportion (%) of $CD3^+/4^+/154^+$ cells ($1.7{\pm}0.5$ vs. $0.3{\pm}0.2$, p=0.038) and the % of $CD3^+/8^+/154^+$ cells ($0.6{\pm}0.2$ vs. $0.1{\pm}0.0$, p=0.024) are significantly higher in study group. The % of $CD3^+/69^+$ cells ($5.6{\pm}1.9$ vs. $1.3{\pm}5.4$, p=0.046) and % of $CD3^+/8^+/69^+$ cells ($4.8{\pm}1.3$ vs. $1.8{\pm}0.2$, p=0.035) among $CD3^+/8^+$ cells are significantly increased in study group. Conclusion: Women with reproductive failures have Th1 propensity with increased T cell activation. These finding means that activated T cell has a harmful effect on early pregnancy and implantation by induction of Th1 immunity.

• Journal of Life Science
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• v.20 no.4
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• pp.503-510
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• 2010

Most allergens have protease activities, suggesting that proteases may be a key link between Th2-type immune reactions in allergic responses. Protease activated receptor (PAR) 2 is activated via the proteolytic cleavage of its N-terminal domain by proteinases. To know the role of PAR2 in Aspergillus protease allergen activated Th2 immune responses in airway epithelial cells, we investigated and compared immune cell recruitment and level of chemokines and cytokines between PAR2 knock out (KO) mice and wild type (WT) mice. There were evident immune cell infiltrations into the bronchial alveolar lavage fluid (BALF) of WT mice, but the infiltrations in PAR2 KO mice were significantly lowered than those of WT mice. The IL-25, TSLP, and eotaxin gene expressions were profoundly increased after Aspergillus protease, but their expression was significantly lowered in PAR2 KO mice in this study. Compared to PAR2 KO mice, OVA specific IgE concentrations in serum of WT mice were quite increased; moreover, the IgE level of PAR2 KO mice was lower than in WT mice. The IL-25 expression by Aspergillus protease stimulation was significantly reduced by p38 specific inhibitor treatment. In this study, we determined that Th2 response was initiated with IL-25 and TSLP mRNA up-regulation in lung epithelial cells via PAR2 after Aspergillus protease allergen treatment.

• International Journal of Contents
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• v.8 no.1
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• pp.74-81
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• 2012

The aim is to investigate the analgesic effect of transcranial direct current stimulation(tDCS) on central neuropathic pain(CNP) in spinal cord contusive rat model. Twenty Sprague-Dawley rats($250{\pm}50$ g, male) were used. Thoracic spinal cord(T10) was contused using New York University(NYU) spinal cord impactor. The animals were randomly assigned to two groups; GroupI: Non-treatment after SCI induction(n=10), GroupII: application of tDCS(0.1 mA, 20 min/time, 2 times/day, 5 days/6week) after SCI induction(n=10). Assess the effect of tDCS using the Basso Beattie Bresnahan(BBB) locomotor rating scales, Touch $test^{TM}$ sensory evaluator(TTSE), Plantar test$^{\circledR}$after contusion at the $2^{nd}$, $3^{rd}$, $4^{th}$, $5^{th}$, $6^{th}$ week and the immunohistochemistric response of c-fos in the thalamus, cerebral cortex after contusion at the $3^{rd}$, $6^{th}$ week after SCI. The scores of BBB scales were significantly different from $3^{rd}$week. TTSE were different significantly over time, but there were no differences at each evaluation times on between-measure time effects. Plantar test were different significantly over time and there were difference at the $4^{th}$, $6^{th}$ week after SCI on between-measure time effects. Also, immunohistochemistric response of c-fos was reduced significantly from $3^{rd}$, $6^{th}$ week after SCI in tDCS group compared with control group in thalamus and cortex. These results identified that tDCS of non-invasive therapeutic method may have beneficial analgesic effect on CNP after SCI with behavioral test and immunohistochemical test.

• 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.23 no.1
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• pp.106-115
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• 2010

Phosphorylated dextran (P-Dex) is an acidic polysaccharide that functions as an immune adjuvant. P-Dex is known to regulate immune response by maintaining a balance between Th1 and Th2 cells in vitro, and thus may also be important in the control of allergic reactions. In the current study, we report the optimum conditions required for the efficient phosphorylation of dextran without toxicity. We found that when dextran was heated at 160${^{\circ}C}$ for 24 h in phosphate buffer (pH 5.0), the resulting P-Dex demonstrated the highest phosphorus content (6.8%). We also report that P-Dex enhances mitogenic activity in mouse splenocytes and induces expression of CD69 and CD86 on the surface of B cells and dendritic cells (DC) in vitro. Oral administration of P-Dex to ovalubmin (OVA)-immunized mice was found to reduce antigen-induced cell proliferation and suppress the expression of CD86 on Th2-inducing DC via exogenous OVA stimulation. P-Dex was also found to increase IL-10 expression in the splenocytes of treated mice. These findings suggest that oral administration of P-Dex increases immunological tolerance and improves the specificity of immunological response to specific antigens.