• The Korean Journal of Physiology and Pharmacology
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• v.13 no.2
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• pp.131-138
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• 2009

The binding of interleukin-6 (IL-6) cytokine family ligands to the gp130 receptor complex activates the Janus kinase (JAK)/ signal transducer and activator of transcription 3 (STAT3) signal transduction pathway, where STA T3 plays an important role in cell survival and tumorigenesis. Constitutive activation of STAT3 has been frequently observed in many cancer tissues, and thus, blocking of the gp130 signaling pathway, at the JAK level, might be a useful therapeutic approach for the suppression of STAT3 activity, as anticancer therapy. AG490 is a tyrphostin tyrosine kinase inhibitor that has been extensively used for inhibiting JAK2 in vitro and in vivo. In this study, we demonstrate a novel mechanism associated with AG490 that inhibits the JAK/STAT3 pathway. AG490 induced downregulation of gp130, a common receptor for the IL-6 cytokine family compounds, but not JAK2 or STAT3, within three hours of exposure. The downregulation of gp130 was not caused by enhanced degradation of gp130 or by inhibition of mRNA transcription. It most likely occurred by translation inhibition of gp130 in association with phosphorylation of the eukaryotic initiation factor-2 a. The inhibition of protein synthesis of gp130 by AG490 led to immediate loss of mature gp130 in cell membranes, due to its short half-life, thereby resulting in reduction in the STAT3 response to IL-6. Taken together, these results suggest that AG490 blocks the STAT3 activation pathway via a novel pathway.

• Parasites, Hosts and Diseases
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• v.51 no.1
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• pp.133-137
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• 2013

This study aimed to measure the levels of interferon-gamma (IFN-${\gamma}$), tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin 1 (IL-1), interleukin 6 (IL-6), and nitrite/nitrate ($NO_x$) in serum of dogs experimentally infected with Rangelia vitalii. Twelve female mongrel dogs were divided into 2 groups; group A (uninfected controls) composed by healthy dogs (n=5) and group B consisting of dogs inoculated with R. vitalii (n=7). Animals were monitored by blood smear examinations, which showed intraerythrocytic forms of the parasite on day 5 post-infection (PI). Blood samples were collected through the jugular vein on days 0, 10, and 20 PI to determine the serum levels of IFN-${\gamma}$, TNF-${\alpha}$, IL-1, IL-6, and $NO_x$. Cytokines were assessed by ELISA quantitative sandwich technique, and $NO_x$ was measured by the modified Griess method. Cytokine levels (IFN-${\gamma}$, TNF-${\alpha}$, IL-1, and IL-6) were increased (P<0.01) in serum of infected animals. Serum levels of $NO_x$ were also increased on days 10 PI (P<0.01) and 20 PI (P<0.05) in infected animals. Therefore, the infection with R. vitalii causes an increase in proinflammatory cytokines and nitric oxide content. These alterations may be associated with host immune protection against the parasite.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.48 no.3
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• pp.265-273
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• 2022

In this study, we investigated whether Korean mistletoe (Viscum album L. var. coloratum) has anti-inflammatory effects that play key roles in the regulation of pathological mechanism of atopic dermatitis (AD). Four kinds of fractions, hexane (HX), ethyl acetate (EA), butanol (BU), and methylene chloride (MC), were used and RAW264.7 mouse macrophages and RBL-2H3 rat basophils were used to measure various inflammatory markers. EA significantly decreased mRNA expression and protein secretion levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and IL-4 but HX did not affect these markers. In addition, BU decreased mRNA expressions of IL-4 and IL-6 whereas MC decreased IL-6 and TNF-α mRNA expressions. As a result, Korean mistletoe can show anti-inflammatory effects by inhibiting the secretion of cytokines related to AD, so it is thought that it will be possible to develop functional cosmetics related to this.

• Journal of Convergence Korean Medicine
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• v.4 no.1
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• pp.19-27
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• 2022

Objectives: TSepsis and subsequent acute lung injury (ALI) is a critical state of health caused by infection or endotoxins. This study was conducted to evaluate the effect of Water Extract of Aconiti Lateralis Preparata Radix (AR) on lipopolysaccharide (LPS)-induced sepsis in C57BL/6 mice. Methods: Male C57BL/6 mice were intraperitoneally injected with LPS to induce sepsis and ALI. AR was orally fed twice at 30 min and 180 min after LPS injection. At 24 h post injection, mice were sacrificed, bronchoalveolar lavage fluid (BALF) and blood was collected, and lung tissue was harvested. Hematoxylin and eosin staining was performed in lung tissues, wet/dry ratio of the lung tissue was measured, and the serum cytokine and chemokine levels were analyzed. Results: AR revoked the LPS-induced pathological changes in lung tissues, such as abnormal histological structures, immune cell infiltration and lung edema. Also, AR suppressed the neutrophil infiltration into the lung which was greatly increased by LPS injection based on the cell content of collected BALF. Serum cytokines and chemokines were measured, and AR reversed the LPS-induced increase of cytokines such as interleukin 1 beta, interleukin 6, tumor necrosis factor alpha and chemokines including C-X-C motif chemokine ligand 1 and 2. Conclusion: TAR showed a protective effect in the pathological progress of LPS-induced ALI. Especially, AR suppressed lung edema and infiltration of neutrophils by inhibiting cytokine and chemokine expressions. Such results demonstrate the potential of AR as a therapeutic agent for sepsis and sepsis-induced ALI.

• Restorative Dentistry and Endodontics
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• v.46 no.1
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• pp.4.1-4.16
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• 2021

Objectives: This study evaluated the biocompatibility and bioactive potential of NeoMTA Plus mixed as a root canal sealer in comparison with MTA Fillapex. Materials and Methods: Polyethylene tubes filled with NeoMTA Plus (n = 20), MTA Fillapex (n = 20), or nothing (control group, CG; n = 20) were inserted into the connective tissue in the dorsal subcutaneous layer of rats. After 7, 15, 30 and 60 days, the specimens were processed for paraffin embedding. The capsule thickness, collagen content, and number of inflammatory cells (ICs) and interleukin-6 (IL-6) immunolabeled cells were measured. von Kossa-positive structures were evaluated and unstained sections were analyzed under polarized light. Two-way analysis of variance was performed, followed by the post hoc Tukey test (p ≤ 0.05). Results: At 7 days, the capsules around NeoMTA Plus and MTA Fillapex had more ICs and IL-6-immunostained cells than the CG. However, at 60 days, there was no significant difference in the IC number between NeoMTA Plus and the CG (p = 0.1137) or the MTA Fillapex group (p = 0.4062), although a greater number of IL-6-immunostained cells was observed in the MTA Fillapex group (p = 0.0353). From 7 to 60 days, the capsule thickness of the NeoMTA Plus and MTA Fillapex specimens significantly decreased, concomitantly with an increase in the collagen content. The capsules around root canal sealers showed positivity to the von Kossa stain and birefringent structures. Conclusions: The NeoMTA Plus root canal sealer is biocompatible and exhibits bioactive potential.

• Journal of Life Science
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• v.17 no.6 s.86
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• pp.791-797
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• 2007

We studied the inhibitory effect of solvent fractions from doenjang on mutagenicity using Salmonella typhimurium TA100 in Ames test. We also investigated the effect of solvent fractions from doenjang on the growth of tumor cells and the production of interleukin-2 (IL-2). The treatment of dichlorormethane and ethylacetate fractions (2.5 mg/assay) from doenjang to Ames test system inhibited aflatoxin B$_1$ (AFB$_1$) induced mutagenicity by 96% and 97%, respectively, and showed a higher antimutagenic effect than other solvent fractions. In case of N-methyl-N'-nitro-N-nitrosoguamidine (MNNG) induced mutagenicity, the ethylacetate fraction showed the highest inhibitory effect (by 75%) among the other sol-vent fractions, although the inhibitory effect was not stronger compared to AFB$_1$ induced mutagenicity. The treatment of dichloromethane and ethylacetate fractions markedly inhibited the growth of Yac-1 (by 80% and 94%, respectively) and sacroma-180 cancer cells (by 60% and 96%, respectively) after 4 days of incubation at 37${\circ}$C. To elucidate the immunological mechanism of antitumor activity of doenjang, spleen cells of Balb/c mouse were exposed to the dichloromethane and ethyl-acetate fractions for 24 hours at 37${\circ}$C . The culture supernatants following the treatment of djchloromethane and ethylacetate factions to spleen cells increased the production of IL-2. These results indicated that the anticarcinogenic effect of doenjang was mediated by the production of IL-2.

• Journal of Microbiology and Biotechnology
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• v.28 no.1
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• pp.115-121
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• 2018

Upon sensing of microbial infections or endogenous danger signals in macrophages, inflammasome signaling plays a significant role in triggering inflammatory responses via producing interleukin (IL)-$1{\beta}$. Recent studies revealed that active caspase-1, a product of the inflammasome complex, causes maturation of inactive pro-IL-$1{\beta}$ into the active form. However, the underlying mechanism by which this leaderless cytokine is secreted into the extracellular space remains to be elucidated. In this study, we demonstrated that prolonged lipopolysaccharide (LPS) treatment to macrophages could trigger the unexpected maturation and extracellular release of IL-$1{\beta}$ through a nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3)-independent manner. Short-term treatment (less than 6 h) of LPS induced robust production of the IL-$1{\beta}$ precursor form inside cells but did not promote the maturation and secretion of IL-$1{\beta}$ in bone marrow-derived macrophages or peritoneal macrophages. Instead, prolonged LPS treatment (more than 12 h) led to a significant release of matured IL-$1{\beta}$ with no robust indication of caspase-1 activation. Intriguingly, this LPS-triggered secretion of IL-$1{\beta}$ was also observed in NLRP3-deficient macrophages. In addition, this unexpected IL-$1{\beta}$ release was only partially impaired by a caspase-1 and NLRP3 inflammasome inhibitor. Collectively, our results propose that prolonged exposure to LPS is able to drive the maturation and secretion of IL-$1{\beta}$ in an NLRP3 inflammasome-independent manner.

• Genomics & Informatics
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• v.14 no.4
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• pp.205-210
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• 2016

Interleukin-10 (IL10) plays an important role in initiating and maintaining an appropriate immune response to non-Hodgkin lymphoma (NHL). Previous studies have revealed that the transcription of IL10 mRNA and its protein expression may be infl uenced by several single-nucleotide polymorphisms in the promoter and intron regions, including rs1800896, rs1800871, and rs1800872. However, the impact of polymorphisms of the IL10 gene on NHL prognosis has not been fully elucidated. Here, we investigated the association between IL10 polymorphisms and NHL prognosis. This study involved 112 NHL patients treated at the National Cancer Center, Korea. The median age was 57 years, and 70 patients (62.5%) were men. Clinical characteristics, including age, performance status, stage, and extra-nodal involvement, as well as cell lineage and International Prognostic Index (IPI), were evaluated. A total of four polymorphisms in IL10 with heterozygous alleles were analyzed for hazard ratios of overall survival (OS) and progression-free survival (PFS) using Cox proportional hazards regression analysis. Diffuse large B-cell lymphoma was the most common histologic type (n = 83), followed by T-cell lymphoma (n = 18), mantle cell lymphoma (n = 6), and others (n = 5). Cell lineage, IPI, and extra-nodal involvement were predictors of prognosis. In the additive genetic model results for each IL10 polymorphism, the rs1800871 and rs1800872 polymorphisms represented a marginal association with OS (p = 0.09 and p = 0.06) and PFS (p = 0.05 and p = 0.08) in B-cell lymphoma patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). These findings suggest that IL10 polymorphisms might be prognostic indicators for patients with B-cell NHL treated with R-CHOP.

• Molecules and Cells
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• v.43 no.5
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• pp.479-490
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• 2020

Interleukin-9 (IL-9) is well known for its role in allergic inflammation. For cancer, both pro- and anti-tumor effects of IL-9 were controversially reported, but the impact of IL-9 on tumor metastasis has not yet been clarified. In this study, IL-9 was expressed as a secretory form (sIL-9) and a membrane-bound form (mbIL-9) on B16F10 melanoma cells. The mbIL-9 was engineered as a chimeric protein with the transmembrane and cytoplasmic region of TNF-α. The effect of either mbIL-9 or sIL-9 expressing cells were analyzed on the metastasis capability of the cancer cells. After three weeks of tumor implantation into C57BL/6 mice through the tail vein, the number of tumor modules in lungs injected with IL-9 expressing B16F10 was 5-fold less than that of control groups. The percentages of CD4⁺ T cells, CD8⁺ T cells, NK cells, and M1 macrophages considerably increased in the lungs of the mice injected with IL-9 expressing cells. Among them, the M1 macrophage subset was the most significantly enhanced. Furthermore, peritoneal macrophages, which were stimulated with either sIL-9 or mbIL-9 expressing transfectant, exerted higher anti-tumor cytotoxicity compared with that of the mock control. The IL-9-stimulated peritoneal macrophages were highly polarized to M1 phenotype. Stimulation of RAW264.7 macrophages with sIL-9 or mbIL-9 expressing cells also significantly increased the cytotoxicity of those macrophages against wild-type B16F10 cells. These results clearly demonstrate that IL-9 can induce an anti-metastasis effect by enhancing the polarization and proliferation of M1 macrophages.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.1061-1070
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• 2004

Chronic oral aphthae, recurrent ulcer and uveitis are the three main festations of Behcet's disease(BD). The aetiopathogenesis of Behcet's disease is still obscure, but herpes simplex virus is one of the possible casual factors. Gamchosasim-tang (Gancaoxiexin-tang), Banhasasim-tang(Banxiaxiexin-tang) and Saenggangsasim-tang( Shengjiangxiexin-tang) are traditional medication in Oriental medicine, that has been used to treat inflammatory disease. Especially, Gamchosasim-tang used to treat Behcet's disease like symptoms. ICR mice were used for this study. The earlobe of the mice were scratched with a needle, then inoculation with 1.0×10/sup 6/ plaque forming units/㎖ of HSV type I. Virus inoculation was performed twice with 10 day interval, followed by 16 weeks of observation. Using the HSV-induced Behcet's disease mouse model, kinds of Sasim-tang were administered variously before and after inoculation. In order to. classify the symptomatic mice as having Behcet's disease like symptoms. We followed the revised Japanese classification with minor modifications. Ulceration of the mice were monitored. In addition, spleen cytokine expression were measured by polymerase chain reaction, ELISA. HSV DNA was detected in HSV inoculation mice. HSV-induced mice treated with kinds of Sasim-tang showed improvement in symptom. In RT-PCR results, IFN-γ was expressed for all groups, IL-2 was expressed for the treated groups, and IL-10 was also expressed. IL-4 was expressed nothing. In ELISA, IL-2 was increased for GSST 2, BSST 2, GSST 2, GSST3 and INF-γ was increased for GSST 2, BSST 2, SSST 2, SSST 3. This model suggest the possible role of immune response to viral infection in the development and activation of Behcet's disease.