• 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.

• 한국어병학회지
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• 제33권1호
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• pp.23-34
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• 2020

In recent years, global warming is causing dramatic environmental changes and deterioration, such as hypoxia, leading to reduced survival rate and growth performance of farmed aquatic animals. Hence, understanding systemic immuno-physiological changes in fish under environmental stress might be important to maximize aquaculture production. In this study, we investigated physiological changes in rainbow trout exposed to hypoxic stress by monitoring changes in blood chemistry, leukocyte population, and expression levels of related cytokine genes. Hematological and serological factors were evaluated in blood obtained from rainbow trout sampled at a dissolved level of 4.6 mg O₂ L^-1 and 2.1 mg O₂ L^-1. Blood and head kidney tissue obtained at each sampling time point were used to determine erythrocyte size, leukocyte population, and cytokine gene expression. The level of LDH and GPT in fish under progressive hypoxia were significantly increased in plasma. Likewise, the (Granulocyte + Macrophage)/lymphocyte ratio (%) of fish exposed to hypoxia was significantly lower than that in fish in the control group. Such changes might be due to the rapid movement of lymphocytes in fish exposed to acute hypoxia. In this study, significant up-regulation in expression levels of IL-1β and IL-6 gene appeared to be involved in the redistribution of leukocytes in rainbow trout. This is the first study to demonstrate the involvement of cytokines in leukocyte trafficking in fish exposed to hypoxia. It will help us understand systemic physiological changes and mechanisms involved in teleost under hypoxic stress.

• Journal of Microbiology and Biotechnology
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• 제26권7호
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• pp.1198-1205
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• 2016

Lactic acid bacteria (LAB) have beneficial effects on intestinal health and skin diseases. Lipoteichoic acid (LTA), a cell wall component of gram-positive bacteria, is known to induce the production of several cytokines such as TNF-α, IL-1β, and IL-8 and affect the intestinal microflora, anti-aging, sepsis, and cholesterol level. In this study, Weissella cibaria was isolated from Indian dairy products, and we examined its immune-enhancing effects. Live and heat-killed W. cibaria did not induce the secretion of immune-related cytokines, whereas LTA isolated from W. cibaria (cLTA) significantly increased the secretion of TNF-α, IL-1β, and IL-6 in a dose-dependent manner. cLTA increased the phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells, p38 mitogen-activated protein kinases, and c-Jun N-terminal kinases in THP-1 cells. The secretion of TNF-α and IL-6 was also increased in the cLTA-treated mouse splenocytes. These results suggest that cLTA, but not W. cibaria whole cells, has immune-boosting potential and can be used to treat immunosuppression diseases.

• IMMUNE NETWORK
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• 제10권5호
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• pp.145-152
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• 2010

Background: The flowers of Inula japonica (Inulae Flos) have long been used in traditional medicine for the treatment of inflammatory diseases. In the present study, we investigated the anti-inflammatory properties of Inulae Flos Extract (IFE). Methods: The anti-inflammatory effects of IFE against nitric oxide (NO), $PGE_2$, TNF-${\alpha}$, and IL-6 release, as well as NF-${\kappa}B$ and MAP kinase activation were evaluated in RAW 264.7 cells. Results: IFE inhibited the production of NO and the expression of inducible nitric oxide synthase (iNOS) in LPS-stimulated RAW264.7 cells. In addition, IFE reduced the release of pro-inflammatory cytokines, such as TNF-${\alpha}$ and IL-6. Furthermore, IFE inhibited the NF-${\kappa}B$ activation induced by LPS, which was associated with the abrogation of $I{\kappa}B-{\alpha}$ degradation and subsequent decreases in nuclear p65 and p50 levels. Moreover, the phosphorylation of ERK, JNK, and p38 MAP kinases in LPS-stimulated RAW 264.7 cells was suppressed by IFE in a dose-dependent manner. Conclusion: These results suggest that the anti-inflammation activities of IFE might be attributed to the inhibition of NO, iNOS and cytokine expression through the down-regulation of NF-${\kappa}B$ activation via suppression of $I{\kappa}B{\alpha}$ and MAP kinase phosphorylation in macrophages.

• BMB Reports
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• 제38권5호
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• pp.571-576
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• 2005

Cytokines are proteins produced by many different cells of the immune system and play a significant role in initiating and regulating the inflammatory process. In this research, an important cytokine, interleukin-10 (IL-10) gene, has been identified and characterized from zebrafish (Danio rerio) genome database. Zebrafish IL-10 is located within a 2690 bp fragment and contains five exons and four introns, sharing the same organization with mammalian IL-10 genes. An open reading frame of 543 bp was found to encode a putative 180 amino acid protein with a signal peptide of 22 amino acids, which shares 29.7-80.9% homology with amino acid sequences of other known IL-10. The signature motif of IL-10 is also conserved in zebrafish IL-10. The predicted transcript was finally confirmed by sequencing of cDNA clones. Multi-tissue reverse transcriptase PCR (RT-PCR) was performed to examine the tissue distribution and expression regulation of this gene in seven organs of normal and lipopolysaccharide (LPS) stimulation zebrafish. The results demonstrated that this gene was expressed slightly in normal kidney, gill and gut, no expression was detected in other four tissues. The expression was clearly upregulated after LPS stimulation. Using the ideal zebrafish model, further study of IL-10 characterization and function may provide insight on the understanding of the innate immune system.

• Advances in Traditional Medicine
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• 제6권3호
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• pp.237-244
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• 2006

Samultang has been believed for prevention and remedy various blood diseases such as menstrual irregularity, anemia, and metrorrhagia. However, the mechanism that accounts for anti-inflammatory effects of the Samultang is still not fully understood. This study was designed to evaluate whether and how the Samultang could modulate the production of pro-inflammatory cytokines in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 treated-human mast cell line, HMC-1. Samultang inhibited the production of tumor necrosis factor $(TNF)-\alpha$, interleukin (IL)-6, granulocyte macrophage colony stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF) in HMC-1. Maximal inhibition rate of $TNF-\alpha$, IL-6, GM-CSF, and VEGF by 0.1 mg/ml Samultang was about $70.73{\pm}3.0%,\;51.49{\pm}4.14%,\;54.03{\pm}2.09%$, and $47.95{\pm}7.86%$, respectively. Samultang partially blocked PMA plus A23187-induced cyclooxygenase (COX)-2 expression. In addition, Samultang inhibited activation of nuclear factor (NF)-kB, and extracellular signal-regulated kinase (ERK) activation. These results suggest that anti-inflammatory effect of Samulatng may be mediated by the suppression of cytokine production and COX-2 activation via down-regulation of NF-kB and ERK activation.

• 대한한방부인과학회지
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• 제23권2호
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• pp.71-84
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• 2010

Purpose: In the theory of traditional medicine, Glenditsia spina(GS) can resolve carbuncle, relive swelling, dispel wind and destroy parasites. This study was designed to investigate the effects of GS on gene expression of ovarian tissue in polycystic ovary syndrome(PCOS) rats. Methods: In this experiment, female rats injected with a single dose of 2 mg estradiol valerate(EV) and GS was given for 5 weeks. The genetic profile for the effects on ovarian tissue in PCOS rats was measured using microarray technique, and the functional analysis on these genes was conducted. Results: 985 genes were increased in control and restored to normal level in GS group. (B), 733 genes were decreased in control group and restored to normal level in GS group. (F). Metabolic pathways related in B group genes were Graft-versus-host disease, Allograft rejection, Autoimmune thyroid disease, Cytokine-cytokine receptor interaction, Small cell lung cancer, Type I diabetes mellitus. Metabolic pathways related in F group genes were Antigen processing and present, Adipocytokine signalling pathway, Focal adhesion, ECM-receptor interaction, Pancreatic cancer, Notch signalling pathway, Tight junction. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as c-Fos, c-Myc, ABL1 related in B group, MAPK8, RASA1, CALR related in F group that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: These results suggest possibility of GS as anti-cancer and anti-hyperplasia drug in PCOS. In addition, the present author also suggests that related mechanisms are involved in suppression of proto-oncogene such as c-Fos, c-Myc and ABL1, and in regulation of cell cycle such as RASA1.

• Biomolecules & Therapeutics
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• 제21권6호
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• pp.435-441
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• 2013

Emodin, a naturally occurring anthraquinone derivative isolated from Polygoni cuspidati radix, has several beneficial pharmacologic effects, which include anti-cancer, anti-diabetic, and anti-inflammatory activities. In this study, the authors examined the effect of emodin on the production of proinflammatory cytokines, such as, tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-6, in mouse bone marrow-derived mast cells (BMMCs) stimulated with phorbol 12-myristate 13-acetate (PMA) plus the calcium ionophore A23187. To investigate the mechanism responsible for the regulation of pro-inflammatory cytokine production by emodin, the authors assessed its effects on the activations of transcriptional factor nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and mitogen-activated protein kinases (MAPKs). Emodin attenuated the nuclear translocation of (NF)-${\kappa}B$ p65 and its DNA-binding activity by reducing the phosphorylation and degradation of $I{\kappa}B{\alpha}$ and the phosphorylation of $I{\kappa}B$ kinase B (IKK). Furthermore, emodin dose-dependently attenuated the phosphorylations of MAPKs, such as, extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAP kinase, and the stress-activated protein kinases (SAPK)/c-Jun-N-terminal kinase (JNK). Taken together, the findings of this study suggest that the anti-inflammatory effects of emodin on PMA plus A23187-stimulated BMMCs are mediated via the inhibition of NF-${\kappa}B$ activation and of the MAPK pathway.

• 생명과학회지
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• 제9권1호
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• pp.50-57
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• 1999

STAT들은 다양한 cytokine이나 성장호르몬 등에 의해 활성화되어 핵으로 빠르게 이동되어 유전자 발현을 조절한다. 우리는 D-raf 유전자의 5' 발현조절영역에서 STAT결합부위 염기서열을 발견하였다. 본 연구는 D-raf 유전자발현조절에 있어서 STAT결합부위의 역할을 형질전환 초파리를 사용하여 조사하였다. STAT결합부위에 염기치환돌연변이를 도입시킨 D-raf promoter부분을 P인자 벡터의 IacZ유전자에 융합시킴으로써 리포터 플라스미드 pDraf-STATmut-lacZ를 제작하였다. 이 리포터 플라스미드를 이용하여 얻은 Draf-STATmut-lacZ형질전환 초파리의 lacZ발현을 발생단계별, 조직별로 조사한 결과, 거의 모든 발생단계에서 정상형 Draf-lacZ 형질전환 초파리의 lacZ발현에 비해 크게 감소하였다. 본 연구결과들은 STAT결합배열 부위가 D-raf유전자발현조절에 있어서 중요한 역할을 함을 개체수준에서 증명하고 있다.