• Journal of Life Science
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• v.28 no.1
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• pp.17-25
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• 2018

In this study, we examined the efficacy of the immune regulation of ${\beta}$-1,3/1,6-glucan and Lactobacillus plantarum LM1004 on atopic dermatitis models. The oral administration of ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 on mice significantly decreased the amount of scratching, leakage to evans blue, and concentrations of serum immunoglobulin E (IgE) and histamine compared with the atopic dermatitis - induced group. When atopic dermatitis was induced, the transcription factors (GATA-3, retinoic acid-related orphan receptor ${\gamma}$ T [$ROR{\gamma}T$]) and cytokines (interleukin-4 [IL-4], IL-17) of Th2 and Th17 cells were overexpressed at the transcriptional level, and they significantly decreased with oral administration of ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004. In addition, ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 were shown to modulate the immune balance by increasing the expression of Th1 and Treg transcription (T-bet, forkhead box p3 [Foxp3]) and cytokines (interferon-${\gamma}$ [IFN-${\gamma}$], transforming growth factor-${\beta}$ [TGF-${\beta}$]). Galectin-9 and filaggrin were significantly lower in the atopic dermatitis - induced group and significantly higher in the ${\beta}$-1,3/1,6-glucan-treated group. In contrast, thymic stromal lymphopoietin (TSLP) was highest in the atopic dermatitis-induced group, while mice that were orally administered ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 showed similar TSLP levels to the control group. These results indicate that ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 have immunomodulatory effects and atopic dermatitis improvement effects in an animal model of atopic dermatitis. Therefore, it is expected that ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 can be used as natural materials in the treatment of atopic dermatitis.

• Journal of Veterinary Clinics
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• v.29 no.4
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• pp.283-296
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• 2012

Allergic contact dermatitis (ACD) is an inflammatory skin disease and regarded as a prototype of T-cell mediated delayed-type hypersensitivity reactions. Poly-${\gamma}$-glutamic acid (PGA) is a biodegradable polymer that is produced by Bacillus subtilis. This study was performed to assess the effects of PGA in a canine model of ACD. ACD was induced on the back of dogs induced by sensitization and repeated application by 2,4-dinitro-1-chlorobenzene (DNCB). Topical treatment of PGA was applied once a day for 12 days and skin biophysical parameters including transepidermal water loss (TEWL), skin hydration, skin pH, skin thickness and erythema index, were measured every two days during experimental periods. Histopathology and immunohistochemistry were performed to evaluate the antiinflammatory effect. In skin biophysical parameters, TEWL, skin hydration, skin thickness and erythema index were significantly increased, with a maximum increase appeared on day 2 (p < 0.05). On the other hand, skin pH was significantly decreased, with a maximum decrease appeared on day 2 (p < 0.01). After the completion of PGA treatment, skin biophysical parameters were significantly reached those of baseline in a time-dependent manner (p < 0.05). In histopathology, marked increases of epidermal thicknesses were induced after DNCB challenge with numerous inflammatory cell infiltrations and edematous changes, decreases of connective tissue occupied regions in dermis. In addition, marked increases of cytokine - tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interferon-${\gamma}$ (IFN-${\gamma}$)-immunoreactivities in the dermis and of apoptotic markers - caspase-3 and PARP-immunoreactivities in the epidermis were observed in DNCB-PBS control as compared with intact control, respectively (p < 0.01). It means, the ACD and related apoptotic changes were induced by DNCB in the present study. However, these ACD induced by DNCB and related apoptosis in epidermis were significantly inhibited by treatment of PGA treated skin, the decreases of infiltrated inflammatory cells and related decreases of pro-inflammatory cytokine immunoreactivities were also observed (p < 0.01). Based on these findings, PGA may have anti-inflammatory and alleviatory effects in the allergic contact dermatitis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.5
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• pp.486-493
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• 2014

Adipocytes are endocrine cells that release bioactive mediators called adipokines. In condition of obesity characterized by low-grade chronic inflammation, adipocytes release inflammatory adipokines, which is related to insulin resistance. Bojungchiseub-tang (BJCST) has been used in symptoms and signs of edema, dampness-phlegm, kidney failure, and so on in Korean medicine. BJCST is also expected to have anti-obesity activities. In the present study, we examined whether BJCST modulate the production of inflammatory adipokines and the activations of the mitogen-activated protein kinases (MAPK) signaling pathway related to induce adipocyte inflammation to elucidate the effects and its mechanism of BJCST on lowering the content of inflammatory adipokines in 3T3-L1 adipocytes. As a result, BJCST suppressed the production of proinflammatory cytokines, tumor necrosis factor (TNF) $-{\alpha}$, interleukin (IL) $-1{\beta}$, IL-6, interferon (IFN) -${\gamma}$, granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1), and the production of other inflammatory mediators, prostaglandin $E_2(PGE_2)$ and nitric oxide(NO)viadownregulationofcyclooxygenase-2(COX-2)andinducible NO synthase (iNOS) gene expressions. In addition, BJCST decreased the phosphorylation of MAPK that promotes the production of inflammatory adipokines in 3T3-L1 mature adipocytes. In conclusion, BJCST could regulate the production of inflammatory adipokines and MAPK signaling pathway related to induction of adipose inflammation.

• Molecules and Cells
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• v.27 no.5
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• pp.577-582
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• 2009

The development of a high-throughput functional genomic screening provides a novel and expeditious approach in identifying critical genes involved in specific biological processes. Here we describe a cell-based cDNA screening system to identify the transcription activators of BiP, an endoplasmic reticulum (ER) chaperone protein. BiP promoter contains the ER stress element which is commonly present in the genes involved in unfolded protein response (UPR) that regulates protein secretion in cells. Therefore, the positive regulators of BiP may also be utilized to improve the recombinant protein production through modulation of UPR. Four BiP activators, including human UDP-glucose:glycoprotein glucosyltransferase 1 (HUGT1), are identified by the cDNA screening. Overexpression of HUGT1 leads to a significant increase in the production of recombinant erythropoietin, interferon ${\gamma}$, and monoclonal antibody in HEK293 cells. Our results demonstrate that the cDNA screening for BiP activators may be effective to identify the novel BiP regulators and HUGT1 may serve as an ideal target gene for improving the recombinant protein production in mammalian cells.

• The Journal of Internal Korean Medicine
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• v.33 no.4
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• pp.387-404
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• 2012

Objectives : This study was to observe anticancer and related immunomodulatory effects of Kwibi-tang extracts (KBTe) on non-small cell lung carcinoma (squamous epithelial carcinoma), NCI-H520, xenograft Balb/c nu-nu nude mice. Methods : Three different dosages of KBTe, 50, 100 and 200 mg/kg were orally administered once a day for 42 days from 11 days after tumor cell inoculation. Six groups, each of 8 mice per group were used in the present study. Changes in body weight, tumor volume and weight, lymphatic organs (spleen and popliteal lymph node), serum interferon (IFN)-${\gamma}$ levels, splenocytes NK cell activity and peritoneal macrophage activities, splenic tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-10 contents were observed with tumor mass and lymphatic organ histopathology to detect anticancer and immunomodulatory effects. The results were compared with a potent cytotoxic anticancer agent, 5-FU (5-Fluorouracil) 30 mg/kg, intraperitoneal treatment (3-day intervals for 42 days, the optimal effective treatment regimes already confirmed). Results & Conclusions : This study suggest that over 50 mg/kg of KBTe showed favorable anticancer effects on the NCI-H520 cell xenograft with immunomodulatory effects. Although relatively lower anticancer effects were observed in KBTe 200 mg/kg treated mice as compared with 5-FU 30 mg/kg treated mice, no meaningful favorable immunomodulatory effects were observed after 5-FU treatment in the present study.

• Tuberculosis and Respiratory Diseases
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• v.73 no.4
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• pp.234-238
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• 2012

Recently, interferon gamma releasing assay has been recommended to compensate the tuberculin skin test (TST) for screening for latent tuberculosis infection (LTBI). Although it improved the detection of LTBI before treatment with tumor necrosis factor blocker, its application to immune suppressed patients is limited. We report a case of peritoneal tuberculosis (TB) developed in a patient who tested positive for TST and QuantiFERON-TB Gold (QFT-G) before infliximab therapy, to emphasize the importance of monitoring during treatment. A 52-year-old woman presented with abdominal distension. She had been diagnosed with seropositive rheumatoid arthritis six years ago. She had started taking infliximab six months ago. All screening tests for TB were performed and the results of all were negative. At admission, the results of repeated TST and QFT-G tests were positive. Histopathological examination confirmed peritoneal TB. The patient started anti-TB therapy and the symptoms were relieved.

• Tuberculosis and Respiratory Diseases
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• v.73 no.4
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• pp.219-223
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• 2012

Background: We investigated the prevalence of latent tuberculosis infection (LTBI) among medical students in South Korea. Methods: Students from one medical school, who were in second- or third-year classes before clerkship course, were enrolled for three consecutive years in the study. A standard questionnaire was given to each participant, and tuberculin skin test (TST), QuantiFERON-TB GOLD In-Tube (QFT-GIT) assay, and chest radiography were performed. Results: A total of 153 participants were enrolled in the study. The mean age of the subjects was $21.9{\pm}0.9$ years, 105 (68.6%) were male, and 132 (86.3%) had been vaccinated with Bacille Calmette-Gu$\acute{e}$rin (BCG). Four students (2.6%) had a history of contact with tuberculosis (TB) patients during medical practice. No abnormal chest radiograph findings were found for any of the subjects. Of the 153 subjects, 23 (15.0%) tested positive for the TST, and 8 (5.2%) tested positive for the QFT-GIT. The agreement between the two tests was determined to be 0.34 using kappa coefficients. Of the four students who had a history of contact with TB patients, only one subject tested positive for both tests, and the other three students tested negative for both tests. Conclusion: A low prevalence of LTBI was found among medical students before clerkship course in South Korea.

• Journal of Microbiology and Biotechnology
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• v.28 no.1
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• pp.12-21
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• 2018

Photorhabdus temperata (PT), a gram-negative bacterium, lives symbiotically within entomopathogenic nematodes. The insecticidal compounds derived from Photorhabdus are used as biopesticides in agriculture. However, the physiological properties are not well characterized. In the course of our screening for neuroprotective and anti-neuroinflammatory substances from natural products, the culture broth of PT showed considerable activities. By activity-guided purification, five anthraquinones, namely, 3-methoxychrysazine (1), 1,3-dimethoxy-8-hydroxy-9,10-anthraquinone (2), 1,3,8-trihydroxy-9,10-anthraquinone (3), 3,8-dihydroxy-1-methoxy-9,10-anthraquinone (4), and 1,3,4-trimethoxy-8-hydroxy-9,10-anthraquinone (5), were isolated from the ethyl acetate fraction of the PT culture broth. Among the isolated compounds, $75{\mu}M$ 3 significantly protected mouse hippocampal neuronal cells (HT22) against 5 mM glutamate-induced cell death via the inhibition of reactive oxygen species production, $Ca^{2+}$ influx, and lipid peroxidation. Additionally, 3 and 4 effectively suppressed the interferon-${\gamma}$-induced neuroinflammation of mouse-derived microglial cells (BV2) at 10 ng/ml, via the reduction of nitric oxide, interleukin-6, and tumor necrosis factor-${\alpha}$. Anthraquinones 3 and 4 derived from the PT culture broth are a potential starting point to discover neuroprotective and anti-neuroinflammatory drug leads. The novel compound 5 is reported for the first time in this study.

• Environmental Analysis Health and Toxicology
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• v.17 no.4
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• pp.325-332
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• 2002

A helper T(Th)1-mediated response is known to enhance cell -mediated immunity, while a Th2-mediated response is associated with the humoral immunity that if elevated IgE levels and eosinophilia. Prostaglandin (PG)E$_2$results in the decreased capability of Iymphocytes to produce Thl cytokines, with a shift toward a Th2 cytokine response. Chlorpyrifos (CPF) has been reported to impair the blastogenesis and response of T Iymphocytes. CPF also induces delayed febrile effects, which results from the activation of COX -PGE$_2$pathway. The purpose of this study is to determine the effort of CPF on the in vitro production of Th cytokines and the role of PGE$_2$on the CPF-induced production of Th cytokines. Splenocytes obtained from male BALB/c mice were pretreated with CPF(0.1, 1, 10 and 100$\mu$M) in the presence of absence of indomethacin or PGE$_2$for 12 h and then were incubated with concanavalin (Con) A for 48 h. These results showed that CPF remarkedly reduced the production of splenic interleukin (IL)-2 and interferon (IFN)-γ in a dose-dependent manner. CPF significantly increased the splenic IL-4 production at low doses (0.1 and 1$\mu$M) but did not affect at high doses (10 and 100 $\mu$M). Indomethacin reduced the CPF-decreased production of IL-2 and IFN-γ in a dose -dependent manner and significantly attenuated the production of IL-4 increased by CPF 0.1 $\mu$M. High dose of CPF significantly reduced the PGE$_2$-decreased production of IL-2 and IFN-γ, while the PGE$_2$- induced production of IL-4 was significantly enhanced by CPF 1 $\mu$M. These findings suggest that CPF nay down-regulate the immune response of Th 1 type by the suppressed production of IL-2 and IFN-γ, with a shift toward a Th2 cytokine response. The CPF-decreased production of Thl cytokines may not be mediated by endogenous PGE$_2$. Also, CPF may attenuate the exogenous PGE$_2$-decreased Th 1 immune response in a dose--dependent manner but may affect dose-independently the PGE$_2$-induced Th2 immune response.

• 한국생물공학회:학술대회논문집
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• 2001.11a
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• pp.193-196
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• 2001

IL-18. formerly known as IGIF(interferon -gamma inducing factor), is structurally IL-l related but functionally IL-12 related pro-inflammatory cytokine. The human IL -18(hIL-lS), like IL-$1{\beta}$, is synthesized as a biologically inactive precursor of 24kDa lacking a signal peptide, and then cleaved into an active mature form by cystein protease IL-$1{\beta}$ converting enzyme (ICE: caspase- 1), We tested if the mature hIL -18 can be expressed and secreted into culture medium by transforming the forming gene construct consisting of a mature hIL-18 gene fused to signal peptide of rice amylase lA. Secondly, we were tested if the pro- IL-18 could be processed into a biologically active form by caspase-l like protease in plant. Cell suspension culture was established from the leaf-derived calli of transgenic tobacco plant. Southern and Northern blot analysis indicated the expression of both pro-hIL-18 and mature hIL-18 plant cells. Western blot analysis introduced the protein products of pro- hIL -18 and mhIL -18 were observed in transigenic cell lines. In addition, the molecular size of recombinant pro-hILl-18 and mhIL-18 were estimated to be 24kDa and 18kDa, respectively. ELISA revealed that the amount of pro- hIL -18 was 1.3ug per gram of fresh weight calli. Moreover, the presence of mhIL-18 was detected in the culture medium and it appeared to be 25ug/L.