• The Korean Journal of Physiology and Pharmacology
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• 제7권5호
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• pp.283-287
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• 2003

While nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) is beneficial for host survival, it is also detrimental to the host. Thus, regulation of iNOS gene expression may be an effective therapeutic strategy for the prevention of unwanted reactions at various pathologic conditions. During the screening process for the possible iNOS regulators, we observed that esculetin is a potent inhibitor of cytokine-induced iNOS expression. The treatment of 3T3-L1 adipocytes with the tumor necrosis factor-${\alpha}$ (TNF) induced iNOS expression, leading to enhanced NO production. TNF-induced NO production was inhibited by esculetin in a dose-dependent manner. Esculetin inhibited the TNF-induced NO production at the transcriptional level through suppression of iNOS mRNA and subsequent iNOS protein expression. These results suggest esculetin, a component of natural products, as a naturally occurring, nontoxic means to attenuate iNOS expression and NO-mediated cytotoxicity.

• Journal of Ginseng Research
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• 제36권4호
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• pp.354-368
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• 2012

Thousands of literatures have described the diverse role of ginseng in physiological processes such as cancer, neurodegenera tive disorders, insulin resistance, and hypertension. In particular, ginseng has been extensively reported to maintain homeostasis of the immune system and to enhance resistance to illness or microbial attacks through the regulation of immune system. Immune system comprises of different types of cells fulfilling their own specialized functions, and each type of the immune cells is differentially influenced and may be simultaneously controlled by ginseng treatment. This review summarizes the current knowledge on the effects of ginseng on immune system. We discuss how ginseng regulates each type of immune cells including macrophages, natural killer cells, dendritic cells, T cells, and B cells. We also describe how ginseng exhibits beneficial effects on controlling inflammatory diseases and microbial infections.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.276.2-276.2
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• 2002

Glycosaminoglycans(PT -Gag) were isolated from the porcine testis. From the PT -Gag. we obtained two different types of Gag fractions using Dowex macroporous Resin MSA-1 column. PT-Gag-1.5% NaCl and PT -Gag-16% NaCl. Various biological activities of the GAGs were examined in aspect of anticoagulant and immunomodulating activity. The anticoagulant activity of the GAGs was evaluated by activated partial thromboplastin time (aPTT ) assay and thrombin time (TT) assay. The GAGs of porcine testis markedly increased the clotting times of both of aPTT and TT. showing that PT-Gag-16% NaCl was more effective than PT-Gag-1.5% NaCl. The immunomodulating activity of the GAGs was examined in relation to regulation of cytokine production of mutine peritoneal macrophages. Treatment with the GAGs promonently enhanced the prodution of cytokines. IFN-${\gamma}$, from macrophages. Taken together. GAGs isolated from porcine testis possess biological functions such as anticoagulant and immunomodulating activity.

• IMMUNE NETWORK
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• 제20권6호
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• pp.45.1-45.16
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• 2020

IL-9 has been reported to play dual roles in the pathogenesis of autoimmune disorders and cancers. The collaboration of IL-9 with microenvironmental factors including the broader cytokine milieu and other cellular components may provide important keys to explain its conflicting effects in chronic conditions. In this review, we summarize recent findings on the cellular sources of, and immunological responders to IL-9, in order to interpret the role of IL-9 in the regulation of immune responses. This knowledge will provide new perspectives to improve clinical benefits and limit adverse effects of IL-9 when treating pathologic conditions.

• IMMUNE NETWORK
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• 제16권1호
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• pp.44-51
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• 2016

Dendritic cells (DCs) are professional antigen presenting cells, and play an important role in the induction of antigen-specific adaptive immunity. However, some DC populations are involved in immune regulation and immune tolerance. These DC populations are believed to take part in the control of immune exaggeration and immune disorder, and maintain immune homeostasis in the body. Tolerogenic DCs (tolDCs) can be generated in vitro by genetic or pharmacological modification or by controlling the maturation stages of cytokine-derived DCs. These tolDCs have been investigated for the treatment of rheumatoid arthritis (RA) in experimental animal models. In the last decade, several in vitro and in vivo approaches have been translated into clinical trials. As of 2015, three tolDC trials for RA are on the list of ClinicalTrial.gov (www.clinicaltrials.gov). Other trials for RA are in progress and will be listed soon. In this review, we discuss the evolution of tolDC-based immunotherapy for RA and its limitations and future prospects.

• Biomolecules & Therapeutics
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• 제20권1호
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• pp.43-49
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• 2012

Stimulation of mast cells through the high affinity IgE receptor (Fc${\varepsilon}$RI) induces degranulation, lipid mediator release, and cytokine secretion leading to allergic reactions. Although various signaling pathways have been characterized to be involved in the Fc${\varepsilon}$RI-mediated responses, little is known about the precious mechanism for the expression of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in mast cells. Here, we report that rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR), reduces the expression of TNF-${\alpha}$ in rat basophilic leukemia (RBL-2H3) cells. IgE or specific antigen stimulation of RBL-2H3 cells increases the expression of TNF-${\alpha}$ and activates various signaling molecules including S6K1, Akt and p38 MAPK. Rapamycin specifically inhibits antigeninduced TNF-${\alpha}$ mRNA level, while other kinase inhibitors have no effect on TNF-${\alpha}$ mRNA level. These data indicate that mTOR signaling pathway is the main regulation mechanism for antigen-induced TNF-${\alpha}$ expression. TNF-${\alpha}$ mRNA stability analysis using reporter construct containing TNF-${\alpha}$ adenylate/uridylate-rich elements (AREs) shows that rapamycin destabilizes TNF-${\alpha}$ mRNA via regulating the AU-rich element of TNF-${\alpha}$ mRNA. The antigen-induced activation of S6K1 is inhibited by specific kinase inhibitors including mTOR, PI3K, PKC and $Ca^{2+}$chelator inhibitor, while TNF-${\alpha}$ mRNA level is reduced only by rapamycin treatment. These data suggest that the effects of rapamycin on the expression of TNF-${\alpha}$ mRNA are not mediated by S6K1 but regulated by mTOR. Taken together, our results reveal that mTOR signaling pathway is a novel regulation mechanism for antigen-induced TNF-${\alpha}$ expression in RBL-2H3 cells.

• Natural Product Sciences
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• 제13권3호
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• pp.207-213
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• 2007

Scutellaria baicalensis is known as a herbal medicine with anti-inflammatory and anti-oxidative activities. However, effect of Scutellaria baicalensis on lupus pathogenesis that is characterized by overproduction of proinflammatory cytokines and abnormalities in regulation, function, and interaction of immune cells remains unclear. We investigated effects of Scutellariae radix methanol extract (SBMeOH) on the production of proinflammatory cytokines and abnormal activation of T cells in vitro in pristane-induced lupus BALB/c mice. These results demonstrated that SBMeOH significantly decreased the LPS-stimulated production of $TNF-{\alpha}$, IL-6, and IL-10 by splenic and peritoneal macrophages and IL-6 and IL-10 by splenocytes from pristane-induced lupus mice. SBMeOH significantly downregulated the Con A-stimulated overproduction of IL-6, IL-10, and $IFN-{\gamma}$ by splenocytes from pristane-induced lupus mice. Also, SBMeOH significantly attenuated the Con A-induced expression of CD4+ T cells and CD69+CD4+ T cells but not CD8+ T cells in pristane-induced lupus mice. Our findings indicate that SBMeOH may ameliorate lupus pathogenic inflammation and autoimmunity via downregulation of proinflammatory cytokine production and abnormal activation of T cells.

• Molecules and Cells
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• 제43권11호
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• pp.964-973
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• 2020

Recent studies have highlighted that early enhancement of the glycolytic pathway is a mode of maintaining the proinflammatory status of immune cells. Thiamine, a wellknown co-activator of pyruvate dehydrogenase complex, a gatekeeping enzyme, shifts energy utilization of glucose from glycolysis to oxidative phosphorylation. Thus, we hypothesized that thiamine may modulate inflammation by alleviating metabolic shifts during immune cell activation. First, using allithiamine, which showed the most potent anti-inflammatory capacity among thiamine derivatives, we confirmed the inhibitory effects of allithiamine on the lipopolysaccharide (LPS)-induced pro-inflammatory cytokine production and maturation process in dendritic cells. We applied the LPS-induced sepsis model to examine whether allithiamine has a protective role in hyper-inflammatory status. We observed that allithiamine attenuated tissue damage and organ dysfunction during endotoxemia, even when the treatment was given after the early cytokine release. We assessed the changes in glucose metabolites during LPS-induced dendritic cell activation and found that allithiamine significantly inhibited glucose-driven citrate accumulation. We then examined the clinical implication of regulating metabolites during sepsis by performing a tail bleeding assay upon allithiamine treatment, which expands its capacity to hamper the coagulation process. Finally, we confirmed that the role of allithiamine in metabolic regulation is critical in exerting anti-inflammatory action by demonstrating its inhibitory effect upon mitochondrial citrate transporter activity. In conclusion, thiamine could be used as an alternative approach for controlling the immune response in patients with sepsis.

• Bulletin of the Korean Chemical Society
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• 제32권11호
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• pp.3893-3898
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• 2011

Cellular uptake of double-stranded DNA (dsDNA) triggers strong innate immune responses via activation of NF-${\kappa}B$ transcription factor. However, the detailed mechanism of dsDNA-mediated innate immune response remains yet to be elucidated. Here, we show that the expression of tazarotene-induced gene 3 (TIG3) is dramatically induced by dsDNA stimulation, and the siRNA-mediated down-regulation of TIG3 mRNA results in significant suppression of dsDNA-triggered cytokine expression. Because TIG3 has been previously shown to physically interact with transglutaminase (TG) 1 to activate TG activity, and TG2 has been shown to induce NF-${\kappa}B$ activity by inducing $I{\kappa}B{\alpha}$ polymerization, we tested whether TG also plays a role in dsDNA-mediated innate immune response. Pre-treatment of TG inhibitors dramatically reduces dsDNA-triggered cytokine induction. We also show that, in HeLa cells, TG2 is the major TG, and TIG3 physically interacts with TG2. Combined together, our results suggest a novel mechanism of dsDNA-triggered innate immune response which is critically dependent on TIG3 and TG2.

• 대한한방소아과학회지
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• 제26권1호
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• pp.36-45
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• 2012

Objectives Perillae Folium (PF) has been widely used in Korean herbal medicines used for treatment of acute and chronic inflammatory diseases, such as rhinitis, asthma, and enteritis. In this study, to investigate the protective effect of PF on type 1 allergic response, we determined whether PF inhibits early or late allergic responses. Methods The effect of PF was analyzed by ELISA,. RT-PCR and Western blot in RBL-2H3 cells. Levels of ${\beta}$-hexosaminidase, interleukin (IL)-4 and TNF-${\alpha}$ were measured using enzyme-linked immunosorbent assays (ELISAs). mRNA levels of cytokines and enzymes were analyzed with RT-PCR. Signal transduction was analyzed with Western blot. Results We found that PF suppressed ${\beta}$-hexosaminidase release in RBL-2H3 by the IgE-DNP-HSA stimulation. PF also significantly inhibited enzymes level, such as COX-1, COX-2, iNOS, and HDC2, along with reduced cytokine levels, such as IL-2, IL-3, IL-4, IL-6, IL-13, and TNF-${\alpha}$ in RBL-2H3. In addition, PF suppressed the phospholyation of ERK1/2, JNK1/2, and $I{\kappa}B{\alpha}$. Conclusions Our results indicate that PF protects against type 1 allergic response and exert an anti-inflammatory effect through the inhibition of degranulation and expression of cytokines and enzymes via the suppression of signal transduction.