• Journal of Microbiology and Biotechnology
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• v.14 no.1
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• pp.81-89
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• 2004

Tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and lymphotoxin-$\alpha$ (LT-$\alpha$, TNF-$\beta$) can initiate and perpetuate human diseases such as multiple sclerosis (MS), rheumatoid arthritis (RA), and insulin-dependent diabetes mellitus (IDDM). TNFs can be blocked by the use of soluble TNF receptors. However, since monomeric soluble receptors generally exhibit low affinity or function as agonists, the use of monomeric soluble receptors has been limited in the case of cytokines such as TNF-$\alpha$, TNF-$\alpha$, interleukin (IL)-1, IL-4, IL-6, and IL-13, which have adapted to a multi component receptor system. For these reasons, very high-affinity inhibitors were created for the purpose of a TNFs antagonist to bind the TNFR and trigger cellular signal by using the multistep polymerase chain reaction method. First, recombinant simple TNFR-Ig fusion proteins were constructed from the cDNA sequences encoding the extracellular domain of the human p55 TNFR (CD120a) and the human p75 TNFR (CD120b), which were linked to hinge and constant regions of human $IgG_1$ heavy chain, respectively using complementary primers (CP) encoding the complementary sequences. Then, concatameric TNFR-Ig fusion proteins were constructed using recombinant PCR and a complementary primer base of recombinant simple TNFR-Ig fusion proteins. For high level expression of recombinant fusion proteins, Chinese hamster ovary (CHO) cells were used with a retroviral expression system. The transfected cells produced the simple concatameric TNFR-Ig fusion proteins capable of binding TNF and inactivating it. These soluble versions of simple concantameric TNFR-Ig fusion proteins gave rise to multiple forms such as simple dimers and concatameric homodimers. Simple TNFR-1g fusion proteins were shown to have much more reduced TNF inhibitory activity than concatameric TNFR-Ig fusion proteins. Concatameric TNFR-Ig fusion proteins showed higher affinity than simple TNFR-Ig fusion proteins in a receptor inhibitor binding assay (RIBA). Additionally, concatameric TNFR-Ig fusion proteins were shown to have a progressive effect as a TNF inhibitor compared to the simple TNFR-Ig fusion proteins and conventional TNFR-Fc in cytotoxicity assays, and showed the same results for collagen induced arthritis (CIA) in mice in vivo.

• Journal of Life Science
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• v.25 no.12
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• pp.1425-1431
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• 2015

The lymphocyte component of the immune system is divided into B lymphocytes and T lymphocytes. B lymphocytes produce antibodies (humoral immunity) via maturation into plasma cells, and T lymphocytes kill other cells or organisms (cellular immunity). A traditional immunological paradigm is that B lymphocyte and T lymphocyte interactions are a one-way phenomenon, with T lymphocytes helping to induce the terminal differentiation of B lymphocytes into immunoglobulin class-switched plasma cells. A deficiency of T lymphocytes was reported to result in defective B lymphocyte function. However, evidence for a reciprocal interaction between B and T lymphocytes is emerging, with B lymphocytes influencing the differentiation and effector function of T lymphocytes. For example, B lymphocytes have been shown to induce direct tolerance of antigen-specific CD8⁺ T lymphocytes and induce T lymphocytes anergy via transforming growth factor-beta (TGF-β) production. The present study showed that LPS-stimulated B lymphocytes inhibited the differentiation of Th1 lymphocytes by inhibiting the production of interleukin-12 (IL-12) from dendritic cells. An interaction between the B lymphocytes and dendritic cells was not needed for this inhibition, and the B lymphocytes did not alter dendritic cell maturation. B lymphocyte-derived soluble factor (BDSF) suppressed the LPS-induced IL-12p35 transcription in the dendritic cells. Overall, these results point to a novel B lymphocyte- mediated immune suppressive mechanism. The findings cast doubt on the traditional paradigm of immunological interactions involving B lymphocyte and T lymphocyte interactions.

• Journal of Applied Biological Chemistry
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• v.59 no.4
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• pp.365-372
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• 2016

The objective of the present study was to evaluate the protective effect of red ginseng (RG) according to steaming time on 150 mM HCl/60 % ethanol induced gastric ulcer models in mice. The sample was divided into 3 groups-G (dried ginseng), RG 4 (steamed 4 h and dried ginseng), RG 6 (steamed 6 h and dried ginseng), and determined through in vitro experiments, such as 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid radical scavenging activity, HPLC analysis, total polyphenol, and flavonoid contents. In vitro experiment results were depended on steaming hours. Based on the results, we chose two samples (G, RG 6) and conducted in vivo experiments. Mice were divided into 5 groups: Nor (normal group), Con (acute gastritis mice treated with distilled water), G (gastris induced by HCl/Ethanol treated with 100 mg/kg G), RG 6 (gastris induced by HCl/ethanol treated with 100 mg/kg RG 6), and SC (gastris induced by HCl/Ethanol treated with 10 mg/kg sucralfate). In our results revealed that RG 6 suppressed elevated reactive oxygen species, and inflammatory related makers, such as cyclooxygenase-2, inducible nitric oxide synthase, tumor necrosis factor alpha, and interleukin-1 beta. In addition, gastric lesion area was improved. These results suggest that RG 6 protects the stomach by attenuating oxidative stress and inflammatory response under gastric ulcer conditions. Therefore, RG 6 should be a potential therapeutic agent for the treatment of acute gastric ulcer.

• Korean Journal of Acupuncture
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• v.39 no.2
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• pp.43-53
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• 2022

Objectives : Paeonia lactiflora Pallas (PLP) have been reported to have pharmacological effects such as anti-inflammatory and analgesic. However, it is not yet known whether PLP extract has anti-inflammatory effect on HaCaT cells, human keratinocyte. Methods : To confirm the anti-inflammatory effect of PLP on keratinocyte, TNF-𝛼/IFN-𝛾-stimulated HaCaT cells were used. HaCaT cells were pre-treated with PLP for 1h before stimulation with TNF-𝛼/IFN-𝛾. Then HaCaT cells were stimulated with TNF-𝛼/IFN-𝛾 for 24 h, the cells and media were harvested to measure the inflammatory cytokines levels. Granulocyte-macrophage colony stimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1), interleukin 1 beta (IL-1𝛽), and TNF-𝛼 were analyzed by enzyme-linked immunosorbent assay (ELISA), and the mRNA expression of thymus and activation-regulated chemokines (TARC), IL-6, and IL-8 were measured by reverse transcription-polymerase chain reaction (RT-PCR). We also investigated the inhibitory mechanism of the mitogen-activated protein kinase (MAPKs) including ERK, JNK, and p38 and nuclear factor-kappaB (NF-𝜅B) by PLP using western blot. Results : PLP did not show cytotoxicity in HaCaT cells. In TNF-𝛼/IFN-𝛾-stimulated HaCaT cells, PLP significantly inhibited the expression of GM-CSF, MCP-1 IL-1𝛽, TNF-𝛼, TARC and IL-6. PLP inhibited the phosphorylation of ERK and translocation of NF-𝜅B into the nucleus. Conclusions : These results indicate that PLP could ameliorate the TNF-𝛼/IFN-𝛾-stimulated inflammatory response through inhibition of MAPK and NF-kB signal pathway. This suggests that PLP could be used beneficial agent to improve skin inflammation.

• Korean Journal of Poultry Science
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• v.41 no.3
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• pp.205-215
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• 2014

The aim of this study was to determine the effects of stocking density and strain on the performance and physiological adaptive responses including the plasma corticosterone content and the level of mRNA expression of pro-inflammatory cytokines and antioxidant enzymes in broiler chicks. A total of 300 birds of two strains (150 Ross strain vs. 150 Cobb strain) aged 3-d old were allotted into two stocking densities (standard stocking density,$0.046m^2/bird$ vs. high stocking density, $0.023m^2/bird$) in battery cages by $2{\times}2$ factorial designs with ten replicates until 35 d of age. There was no significant strain effect on body weight, feed intakes and feed to gain ratio and the relative organ weights. However body weight, feed intakes and relative organ weight were found to be significantly (P<0.05) affected by the effect of stocking density. Plasma corticosterone level was not affected by both stocking density and strain effects. Hepatic mRNA expression of pro-inflammatory cytokines including interleukin-$1{\beta}$ (IL-$1{\beta}$), IL-6, IL-18 and interferon-gamma (IFN-${\gamma}$) was not significantly changed by the effects of strain and stocking density. However, the mRNA expression of glutathione peroxidase (GPX) was affected by strain, showing that Ross strain decreased (P<0.05) the GPX expression. With respect to the effect of stocking density, there was a significant (P<0.05) increase in superoxide dismutase (SOD) and catalase (CAT) and GPX mRNA expression in the liver from high stocking density group. Splenic pro-inflammatory cytokine expression was not also affected by stocking density and strain, except that IL-18 mRNA significantly (P<0.05) decreased in Cobb strain under high stocking density. The mRNA expression of SOD and CAT was significantly (P<0.05) affected by the effects of stocking density and strain. In conclusion, growth performance was not affected by strain but stocking density. Although mRNA expression of major pro-inflammatory cytokines was not changed by stocking density and strain, antioxidant enzyme was significantly affected by stocking density, strain or even organ in birds under summer conditions. More detailed studies still needed to be explored to elucidate the effects of environmental conditions and genetic background on physiological responses in birds.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.8
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• pp.1090-1098
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• 2016

The anti-inflammatory effects of ethanol extract from Grateloupia crispata (GCEE) were investigated in lipopolysaccharide (LPS)-stimulated murine macrophages. Anti-inflammatory effects were detected by enzyme-linked immunosorbent assay, Western blotting, and immunohistochemistry. There was no cytotoxic effect on proliferation of macrophages treated with GCEE compared to the control. GCEE significantly inhibited production of pro-inflammatory cytokines [interleukin (IL)-6, tumor necrosis $factor-{\alpha}$, and $IL-1{\beta}$] as well as nitric oxide in LPS-stimulated RAW 264.7 cells. In addition, GCEE suppressed expression of inducible nitric oxide synthase, cyclooxygenase-2, and nuclear $factor-{\kappa}B$ in a dose-dependent manner. GCEE significantly reduced activation of mitogen-activated protein kinases. In the in vivo test, evaluation of anti-inflammatory activity of GCEE was performed using croton oil-induced ear edema in ICR mice. Oral administration of 10 mg/kg to 250 mg/kg of GCEE significantly reduced ear edema in a dose-dependent manner compared to croton oil-induced mice. Moreover, GCEE reduced ear thickness and the number of mast cells compared to croton oil-induced mice in the histological analysis. These data suggest that GCEE could be used as a potential source for anti-inflammatory agents.

• Journal of Life Science
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• v.27 no.2
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• pp.187-193
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• 2017

As a part of ongoing research to elucidate and characterize antiinflammatory nutraceuticals, the crude extracts from Atriplex gmelinii C. A. Mey. and their solvent-partitioned fractions were tested for their antiinflammatory potential in lipopolysaccharide (LPS)-stimulated RAW 264.7 mouse macrophages. The crude extracts of A. gmelinii C. A. Mey. were fractioned according to polarity with n-hexane, 85% aqueous methanol (85% aq. MeOH), n-butanol, and $H_2O$. Their antiinflammatory activities were investigated in LPS-induced inflammation in mouse macrophages by measuring nitric oxide (NO) generation and mRNA expression of inflammation mediators, namely, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-$1{\beta}$ ($IL-1{\beta}$), and IL-6. As a result, we confirmed that the crude extracts of A. gmelinii C. A. Mey. inhibited LPS-stimulated NO production and mRNA expression of iNOS and COX-2 as important inflammatory factors. The inhibition of NO production through the downregulation of important inflammatory factors such as iNOS, COX-2, $IL-1{\beta}$, and IL-6 was found by treatment with all solvent-partitioned fractions. Among all tested fractions, 85% aq. MeOH showed the strongest antiinflammatory response. Based on the current results, A. gmelinii C. A. Mey. was suggested to possess natural antiinflammatory components, indicating that it could be used as a valuable source of antiinflammatory substances.

• Korean Journal of Psychosomatic Medicine
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• v.28 no.2
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• pp.177-184
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• 2020

Objectives : Postpartum depression is known to occur in 10-15% of mothers. The concentration of cytokine varies depending on stress, depression, pregnancy and general medical conditions. We hypothesized that the concentration of cytokines may be related to reproduction and childbirth, and that women with postpartum depression would show alterations in cytokines levels. Methods : A total of 104 pregnant women were selected as subjects, and 60 non-pregnant women were selected as normal controls. Symptoms of depression were evaluated in the pregnant study subjects using the diagnostic criteria outlined in the Edinburgh Postnatal Depression Scale (EPDS). The pregnant subjects were divided into three groups perinatal non-depression controls (n=61), postpartum depression-recovery (n=18), and postpartum depression (n=25). Results : The plasma concentration of TGF-β1, IGF-1 was higher in the pregnant group than in non-pregnant controls (TGF-β1 ; p<0.01, IGF-1 ; p=0.026). At 24 weeks of pregnancy and 6 weeks of delivery, there were no significant differences in the plasma concentration of TGF-β1, IGF-1, β-NGF, IL-2, IL-4, IL-6, IFN-γ, TNF-α between the three groups. There was no statistically significant difference in all three groups during the course of depression in pregnant women. Conclusions : This study found significant difference in plasma cytokines concentrations between non-pregnant controls and perinatal non-depression controls.

• BMB Reports
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• v.47 no.9
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• pp.512-517
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• 2014

In this study, we showed that Mycobacterium abscessus MAB2560 induces the maturation of dendritic cells (DCs), which are representative antigen-presenting cells (APCs). M. abscessus MAB2560 stimulate the production of pro-inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor (TNF)-${\alpha}$, IL-$1{\beta}$, and IL-12p70] and reduce the endocytic capacity and maturation of DCs. Using $TLR4^{-/-}$ DCs, we found that MAB2560 mediated DC maturation via Toll-like receptor 4 (TLR4). MAB2560 also activated the MAPK signaling pathway, which was essential for DC maturation. Furthermore, MAB2560-treated DCs induced the transformation of $na\ddot{i}ve$ T cells to polarized $CD4^+$ and $CD8^+$ T cells, which would be crucial for Th1 polarization of the immune response. Taken together, our results indicate that MAB2560 could potentially regulate the host immune response to M. abscessus and may have critical implications for the manipulation of DC functions for developing DC-based immunotherapy.

• Journal of Ginseng Research
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• v.44 no.6
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• pp.790-798
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• 2020

Background: Beneficial effects of Korean Red Ginseng (KRG) on polycystic ovarian syndrome (PCOS) remains unclear. Methods: We examined whether pretreatment (daily from 2 hours before PCOS induction) with KRG extract in water (KRGE; 75 and 150 mg/kg/day, p.o.) could exert a favorable effect in a dehydroepian-drosterone (DHEA)-induced PCOS rat model. Results: Pretreatment with KRGE significantly inhibited the elevation of body and ovary weights, the increase in number and size of ovarian cysts, and the elevation of serum testosterone and estradiol levels induced by DHEA. Pretreatment with KRGE also inhibited macrophage infiltration and enhanced mRNA expression levels of chemokines [interleukin (IL)-8, monocyte chemoattractant protein-1), proinflammatory cytokines (IL-1β, IL-6), and inducible nitric oxide synthase in ovaries induced by DHEA. It also prevented the reduction in mRNA expression of growth factors (epidermal growth factor, transforming growth factor-beta (EGF, TGF-β)) related to inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cell pathway and stimulation of the nuclear factor erythroid-derived 2-related factor 2 pathway. Interestingly, KRGE or representative ginsenosides (Rb1, Rg1, and Rg3(s)) inhibited the activity of inflammatory enzymes cyclooxygenase-2 and iNOS, cytosolic p-IκB, and nuclear p-nuclear factor kappa-light-chain-enhancer of activated B in lipopolysaccharide-induced RAW264.7 cells, whereas they increased nuclear factor erythroid-derived 2-related factor 2 nuclear translocation. Conclusion: These results provide that KRGE could prevent DHEA-induced PCOS via antiinflammatory and antioxidant activities. Thus, KRGE may be used in preventive and therapeutic strategies for PCOS-like symptoms.