• 약학회지
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• 제54권4호
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• pp.232-239
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• 2010

Stems and roots of Acanthopanax koreanum Nakai were extracted with water and treated on immune cells in order to determine their immunomodulatory activites. Various Th-1 type cytokines were measured using ELISA including interleukin (IL)-2, IL-12, interferon-gamma (IFN-$gamma$), and tumor necrosis factor-alpha (TNF-$\alpha$) secreted by dendritic cells, T-cells, intestinal epithelial cells, natural killer cells, and macrophages. As a result, there was a significant increase in IL-12 and IFN-$\gamma$, secretion, but there was no change in the secretion of TNF-$alpha$. Additionally T-cells slightly increased the secretion of IL-2, but there was a significant increase of IL-2 in intestinal epithelial cells. Therefore, our results suggest that A. koreanum Nakai may act as an immunomodulator by stimulating the cell-mediated immunity which can help the immune system defend against infections or cancer cells.

• 한국식품영양학회지
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• 제21권3호
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• pp.275-282
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• 2008

Hot-water($100^{\circ}C$) and cold-water($4^{\circ}C$) extracts of Taraxacum officinale root were assessed for the effects of innate and adaptive immune responses in mice. Hot water extracts(TO-100) and cold water extracts(TO-4) did not affect the viability of macrophages at concentrations below to 18 mg/ml and 8 mg/ml, respectively. The thioglycollate-induced macrophages cultured with TO-100 and TO-4 produced a significantly higher quantity of various cytokines, such as IL-6 and IL-12, than those treated with medium. This shows that the extracts potently stimulated the innate immune response. When mice were subcutaneously immunized(sc) with OVA+FIA(Freund's incomplete adjuvant)-emulsified TO-100, TO-100 did not affect the production of IgE, but enhanced the production of IgG1, IgG2a and IgG2b. The culture supernatant obtained from the splenocytes of mice treated with OVA+FIA-emulsified TO-100 also evidenced elevated levels of both OVA-specific Th1-type(IFN-$\gamma$) and Th2-type cytokines(IL-4, IL-6 and IL-10). These results suggested that TO-100 can modulate the immune responses to allergens in mice.

• Journal of Microbiology and Biotechnology
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• 제26권2호
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• pp.432-439
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• 2016

Shiga toxins (Stxs) produced by Shiga toxin-producing Escherichia coli (STEC) strains are major virulence factors that cause fatal systemic complications, such as hemolytic uremic syndrome and disruption of the central nervous system. Although numerous studies report proinflammatory responses to Stx type 1 (Stx1) or Stx type 2 (Stx2) both in vivo and in vitro, none have examined dynamic immune regulation involving cytokines and/or unknown inflammatory mediators during intoxication. Here, we showed that enzymatically active Stxs trigger the dissociation of lysyl-tRNA synthetase (KRS) from the multi-aminoacyl-tRNA synthetase complex in human macrophage-like differentiated THP-1 cells and its subsequent secretion. The secreted KRS acted to increase the production of proinflammatory cytokines and chemokines. Thus, KRS may be one of the key factors that mediate transduction of inflammatory signals in the STEC-infected host.

• IMMUNE NETWORK
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• 제13권4호
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• pp.123-132
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• 2013

Obesity is consistently increasing in prevalence and can trigger insulin resistance and type 2 diabetes. Many lines of evidence have shown that macrophages play a major role in inflammation associated with obesity. This study was conducted to determine metformin, a widely prescribed drug for type 2 diabetes, would regulate inflammation through down-regulation of scavenger receptors in macrophages from obesity-induced type 2 diabetes. RAW 264.7 cells and peritoneal macrophages were stimulated with LPS to induce inflammation, and C57BL/6N mice were fed a high-fat diet to generate obesity-induced type 2 diabetes mice. Metformin reduced the production of NO, $PGE_2$ and pro-inflammatory cytokines ($IL-1{\beta}$, IL-6 and $TNF-{\alpha}$) through down-regulation of $NF-{\kappa}B$ translocation in macrophages in a dose-dependent manner. On the other hand, the protein expressions of anti-inflammatory cytokines, IL-4 and IL-10, were enhanced or maintained by metformin. Also, metformin suppressed secretion of $TNF-{\alpha}$ and reduced the protein and mRNA expression of $TNF-{\alpha}$ in obese mice as well as in macrophages. The expression of scavenger receptors, CD36 and SR-A, were attenuated by metformin in macrophages and obese mice. These results suggest that metformin may attenuate inflammatory responses by suppressing the production of $TNF-{\alpha}$ and the expressions of scavenger receptors.

• Journal of Ginseng Research
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• 제30권4호
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• pp.181-187
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• 2006

Protopanaxadiol (PPD) is a mixture of protopanaxadiol type saponins with a dammarane skeleton, from Korean red ginseng (Panax ginseng C.A. Meyer; Araliaceae). Korean ginseng is well-known herb to treat almost all kinds of diseases in Oriental medicine. This herb was particularly prescribed for treatment various inflammatory diseases, including rheumatoid arthritis, atherosclerosis, and diabetes mellitus, for centuries. To understand the efficacy of ginseng against inflammatory diseases, we aimed to show anti-inflammatory activities of the PPD in murine macrophage cell line, RAW264.7 cells using nitric oxide (NO) production assay and the expressions of pro-inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$), and IL-6, and monocyte chemotactic protein-1 (MCP-1). We found that PPD saponin significantly blocked LPS ($1{\mu}g/ml$)-induced NO production in a dose-dependent manner. In addition, PPD abrogated the expressions of LPS-induced pro-inflammatory cytokines, such as IL-$1{\beta}$ and MCP-1. Moreover, cyclooxygenase (COX)-2, a critical enzyme to produce prostaglandin E2 (PGE2), was significantly inhibited by PPD in LPS-activated RAW264.7 cells. Taken together, these results suggested that anti-inflammatory efficacy of Korean red ginseng on inflammatory diseases is, at least, due to the NO inhibitory activity and the inhibition of the expressional level of inflammatory cytokines and/or mediators.

• Korean Journal of Acupuncture
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• 제29권3호
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• pp.406-420
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• 2012

Objectives : Scutellaria barbata has been widely used in oriental medicine used for treatment of acute and chronic inflammatory diseases. In this study, to investigate the protective effect of Scutellaria barbata on type I allergic response, we determined whether Scutellaria barbata inhibits early or late allergic responses. Methods : To assess the effect of Scutellaria barbata Pharmacopuncture Extract(SB) in RBL-2H3 cells, we investigated the levels of the markers of degranulation such as ${\beta}$-hexosaminidase and histamine, inflammatory mediator such as IL-4, TNF-${\alpha}$, PGE2 and cysLT, and mRNA expression of cytokines and enzymes. In addition, we determined the levels of intracellular ROS by DCFH-DA assay and the free radical scavenging activity by DPPH method. Results : We found that SB suppressed the release of ${\beta}$-hexosaminidase and histamine and the production of IL-4, TNF-${\alpha}$, PGE2 and cysLT in RBL-2H3 by the antigen stimulation. SB also significantly inhibited the enzyme mRNA expressions, such as HDC2, COX-1, COX-2, 5-LOX and iNOS2, along with reduced cytokine mRNA expressions, such as IL-$1{\beta}$, IL-2, IL-3, IL-4, IL-5, IL-6, IL-13, TNF-${\alpha}$ and GM-CSF in RBL-2H3. In addition, SB suppressed the levels of intracellular ROS. Conclusions : Our results indicate that SB protects against type I allergic response and exert an anti-inflammatory effect through the inhibition of degranulation, inflammatory mediator release and mRNA expression of cytokines and enzymes.

• Journal of Ginseng Research
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• 제33권2호
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• pp.149-154
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• 2009

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and progressive cartilage and bone erosion. Korean red ginseng (KRG) has been shown to have an anti-inflammatory effect by inhibiting the secretion of inflammatory cytokines like $TNF-{\alpha}$, IL-1, -6, and -8, and $IPN-{\gamma}$. In this study, whether KRG extract has an inhibitory effect on the collagen-inducible development of arthritis in DBA/1J mice was investigated. To induce arthritis, type II collagen emulsified in Complete Freund's Adjuvant was intradermally injected into the base of the tails of mice. Three weeks after the initial injection, a booster injection of type II collagen emulsified in Incomplete Freund's Adjuvant was administered. The oral administration of KRG extract for 8${\sim}$10 weeks at the dose of 300 mg/kg (three days a week) inhibited the development of arthritis in the experimental group, compared to the control group which was given saline. While the administration of KRG extract three times a week demonstrated both preventive and inhibitory effects, the administration of KRG extract once a week had little inhibitory effect. In other studies, the regimen of KRG administration has been shown to decrease the plasma level of inflammatory cytokines like IL-8 and TNF-${\alpha}$, but the plasma levels of these cytokines were not decreased in the present study. The results of the present study suggest that KRG has preventive and inhibitory effects on collagen-induced arthritis.

• Genomics & Informatics
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• 제9권3호
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• pp.114-120
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• 2011

Chronic inflammation has been implicated as one of the important etiological factors in insulin resistance and type 2 diabetes mellitus (T2DM). To investigate the role of anti-inflammatory cytokines in the development of T2DM, we conducted a case-control study to assess the association between IL4/IL4R polymorphisms and disease risk. We firstly identified single nucleotide poly-morphisms (SNP) at IL4 and IL4RA loci by sequencing the loci in Korean participants. Case-control studies were conducted by genotyping the SNPs in 474 T2DM cases and 470 non-diabetic controls recruited from community-based cohorts. Replication of the associated signals was performed in 1,216 cases and 1,352 controls. We assessed effect of IL4 -IL4RA interaction on T2DM using logistic regression method. The functional relevance of the SNP associated with disease risk was determined using a reporter expression assay. We identified a strong association between the IL4 promoter variant rs2243250 and T2DM risk (OR=0.77; 95% CI, 0.67~0.88; p=$1.65{\times}10^{－4}$ in the meta-analysis). The reporter gene expression assay demonstrated that the presence of rs2243250 might affect the gene expression level with ~1.5-fold allele difference. Our findings contribute to the identification of IL4 as a T2D susceptibility locus, further supporting the role of anti-inflammatory cytokines in T2DM disease development.

• IMMUNE NETWORK
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• 제14권6호
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• pp.307-320
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• 2014

Mycobacterium scrofulaceum is an environmental and slow-growing atypical mycobacterium. Emerging evidence suggests that M. scrofulaceum infection is associated with cervical lymphadenitis in children and pulmonary or systemic infections in immunocompromised adults. However, the nature of host innate immune responses to M. scrofulaceum remains unclear. In this study, we examined the innate immune responses in murine bone marrow-derived macrophages (BMDMs) infected with different M. scrofulaceum strains including ATCC type strains and two clinically isolated strains (rough and smooth types). All three strains resulted in the production of proinflammatory cytokines in BMDMs mediated through toll-like receptor-2 and the adaptor MyD88. Activation of MAPKs (extracellular signal-regulated kinase 1/2, and p38, and c-Jun N-terminal kinase) and nuclear receptor (NF)-${\kappa}B$ together with intracellular reactive oxygen species generation were required for the expression of proinflammatory cytokines in BMDMs. In addition, the rough morphotypes of M. scrofulaceum clinical strains induced higher levels of proinflammatory cytokines, MAPK and NF-${\kappa}B$ activation, and ROS production than other strains. When mice were infected with different M. scrofulaceum strains, those infected with the rough strain showed the greatest hepatosplenomegaly, granulomatous lesions, and immune cell infiltration in the lungs. Notably, the bacterial load was higher in mice infected with rough colonies than in mice infected with ATCC or smooth strains. Collectively, these data indicate that rough M. scrofulaceum induces higher inflammatory responses and virulence than ATCC or smooth strains.

• 동의생리병리학회지
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• 제19권5호
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• pp.1323-1329
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• 2005

This study was carried out to know the immunity responses of Sogyughwalhyel-tanggami(SGHHT) to on Rheumatoid Arthritis in Collagen-induced Arthritis(CIA) Mice. Various experimental were peformed to analyse the immunity effects of SGHHT. The cytotoxicity against mLFCs was not measured. The production of pro-inflammatory cytokines $IL-1{\beta}$, IL-6, $TNF-\alpha$ were reduced in hFLSs. The production of pro-inflammatory cytokines $IFN-\gamma$, IgG3, IgG2b, IgM were reduced. Comparison of the results for this study showed that SGHHT had immunomodulatory effects of suppressing or enhancing. So we expect that SGHHT should be used as a effective drugs for not only rheumatoid arthritis but also another auto-immune disease. Therefore we have to survey continuously in looking for the effective substance and mechanism in the future.