• Bioinformatics and Biosystems
• /
• v.2 no.2
• /
• pp.71-74
• /
• 2007

Cell phenotypes are determined by groups of functionally related genes. Microarray profiling of gene expression provides us response of cellular state to its perturbation. Several methods for uncovering a cellular network show reliable network reconstruction. In this study, we present reconstruction of genetic regulatory network of inflammation bowel disease in human peripheral blood mononuclear cell. The microarray based on Affymetrix Gene Chip Human Genome U133 Array Set HG-U133A is processed and applied network reconstruction algorithm, ARACNe. As a result, we will show that inferred network composed of 450 nodes and 2017 edges is roughly scale-free network and hierarchical organization. The major hub, CCNL2 (cyclin A2), in inferred network is shown to be associated with inflammatory function as well as apoptotic function.

• Animal cells and systems
• /
• v.14 no.4
• /
• pp.275-282
• /
• 2010

Chunghyul-dan (CHD) is a combinatorial drug known to exert anti-inflammatory effects in endothelial cells. In this study, we employed global transcriptional profiling using cDNA microarrays to identify molecular mechanisms responsible for the anti-inflammatory activity of CHD in endothelial cells. An analysis of the microarray data revealed that transcript levels of monocyte chemotactic protein-1 (MCP-1), vascular cell-adhesion molecule-1 (VCAM-1) and activated leukocyte cell-adhesion molecule were dramatically altered in CHD-treated endothelial cells. These changes in gene expression were confirmed by RT-PCR, Western blotting and ELISA. Chronic CHD treatment also appeared to decrease MCP-1 secretion, probably as a result of decreased MCP-1 expression. In addition, we determined that chronic CHD treatment inhibited lipopolysaccharide-stimulated adhesion of THP-1 leukocytes to endothelial cells. The inhibitory effect of CHD on LPS-stimulated adhesion resulted from downregulation of VCAM-1 expression. Transmigration of THP-1 leukocytes through endothelial cells was also inhibited by chronic CHD treatment. In conclusion, CHD controls a variety of inflammatory activities by regulating MCP-1 and VCAM-1 gene expression.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.29 no.2
• /
• pp.174-179
• /
• 2015

Transcription factor, Nrf2 was well known to protect cell from oxidative stress by up-regulating it's dependent anti-oxidative genes such as HO-1 and NQO1. Cheongjogupye-tang (CJGPT), a traditional herbal formula was originally recorded in 『EuiMunBeopRyul』, still having been used to treat pulmonary disease such as asthma and pulmonary inflammation, in Eastern Asian countries. However, the underlying therapeutic mechanisms remain elusive. The purpose of this study is to investigate the anti-inflammatory or anti-oxidative effects of CJGPT on the RAW 264.7 cells. To examine the anti-inflammatory or anti-oxidative effects of CJGPT, MTT assay, immunoblotting, RT-PCR and reporter gene assays were performed. Although CJGPT slightly suppressed the nuclear NF-κB expression, it did not decreased the expression of pro-inflammatory genes in LPS-stimulated RAW 264.7 cells. Moreover, it did not increased the transcriptional activity of NF-κB in reporter gene assay. However, CJGPT upregulated the nuclear expression of Nrf2, as well as increased the expression of Nrf2-dependent genes such as HO-1 and NQO1. In addition, CJGPT incresed the transcriptional activity of Nrf2. Taken together, our results showed that CJGPT exerts functions as an anti-oxidant mainly by activating Nrf2.

• Journal of Ginseng Research
• /
• v.35 no.1
• /
• pp.111-123
• /
• 2011

To investigate the effects of repeated immobilization-stress challenge on the the hypothalamic-pituitary-adrenal axis, the genomic transcriptome in the adrenal cortex of immobilization-stressed mouse was analyzed by using a cDNA microarray. Mice were subjected to immobilization stress for 2 h per day for 5 consecutive d. With a 4.0-fold cutoff of arbitrary criteria, the expression levels of 168 out of 41,174 genes were significantly modulated in the adrenal cortex by stress when comparing the control and experimental groups. These genes were related to apoptosis, cell cycle, immune response, inflammatory responses, and signal transduction, and thus may be used as potential targets for the development of therapeutics for chronic stress or depression. Six significant genes among these were selected for real time polymerase chain reaction analysis to confirm the change of their expression levels. The gene for phospho 1 was also further investigated because its expression showed the greatest fold-change.

• Journal of Microbiology
• /
• v.39 no.3
• /
• pp.186-194
• /
• 2001

Scrub typhus, caused by Orientia tsutsugamushi infection, is clinically and histopathologically characterized by local as well as systemic inflammatory reactions, indicating that orientiae induce mechanisms that amplify the inflammatory response. To reveal underlying mechanisms of chemoattraction and activation of responding leukocytes, expression of chemokine and tumor necrosis factor alpha (TNF-$\alpha$) genes in murine peritoneal macrophages after infection with the obligate intracellular bacterium Ο.tsutsugamushi was investigated. The genes that were unregulated included macrophage inflammatory proteins l$\alpha$/$\beta$(MIP-l$\alpha$/$\beta$), MIP-2, monocyte chemoattractant protein 1(MCP-1), RANTES (regulated upon activation, normal T-cell expressed and secreted), gamma-interferon-inducible protein 10(IP-10) and TNF-$\alpha$. Peak expression of these chemokines and TNF-$\alpha$ was observed between 1 and 3 h after infection. These responses returned to or approached baseline preinfection levels 6 h after challenge. Semiquantitative reverse transcription (RT)-PCR analysis revealed dramatic Increases during infection in the steady-state levels of mRNA ceding for the inhibitory subunit of NF-kB (IkB$\alpha$), whose transcription is enhanced by binding of NF-kB within the IkB$\alpha$promoter region. Thus, Ο. tsutsugamushi appears to be a stung inducer of chemokines and TNF-$\alpha$ which may significantly contribute to inflammation and tissue damage observed in scrub typhus by attracting and activating phagocytic leukocytes.

• Journal of Embryo Transfer
• /
• v.31 no.4
• /
• pp.323-333
• /
• 2016

Pro-inflammatory cytokines, interleukin-$1{\beta}$(IL1B), IL6, and tumor necrosis factor-alpha (TNF), are known to play important roles in regulating the endometrial function in the uterus during the estrous cycle and pregnancy in several species. However, the expression and function of these cytokines and their receptors in the uterine endometrium during the estrous cycle have not been studied in pigs. Thus, this study determined the expression and regulation of IL1B, IL6, TNF and their respective receptors, IL1R1, IL1RAP, IL6R, GP130, TNFRSF1A, and TNFRSF1B during the estrous cycle in pigs. To analyze levels of each gene expression in the uterine endometrium we obtained from endometrial tissues on Days 0, 3, 6, 9, 12, 15, and 18 of the estrous cycle. Real-time RT-PCR analysis showed that levels of IL1B, IL1RAP, IL6R, GP130, TNF, TNFRSF1A, and TNFRSF1B mRNAs were highest on Day 15 or 18 of the estrous cycle, which corresponds to the proestrus period. Levels of IL1R1 were highest on Day 0, while levels of IL6 were biphasic with high levels on Day 6 and Day 15. The abundance of IL1B, IL6, IL6R, and TNF mRNAs was decreased by progesterone, while levels of GP130 were increased by progesterone in endometrial tissue explants. These results showed that expression of pro-inflammatory cytokines and their receptors changed stage-specifically during the estrous cycle and regulated by progesterone in the uterine endometrium in pigs, suggesting that these pro-inflammatory cytokines may be involved in the regulation endometrial function during the estrous cycle in pigs.

• Journal of The Korean Society of Integrative Medicine
• /
• v.9 no.1
• /
• pp.163-171
• /
• 2021

Purpose : The purpose of this study was to examine the anti-inflammatory effects of Sparassis crispa (SC). SC is a well-known traditional herbal remedy and its mushroom is used for treatment of inflammation. Many diseases that are increasing recently have characteristics of inflammatory diseases. Researchers are finding bioactive substances from natural products that can promote treatment and prevention of inflammation. We investigated the effect of water extracted from SC on the expression of effector genes involved in the function of RAW 264.7 cells. Methods : Effects of RAW 264.7 cells on cell viability, antioxidation, and mRNA expression were examined using water extracts from SC. A 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay was performed to determine the effect of water extracts from SC on cell viability in RAW 264.7 cells. Inflammation of RAW 264.7 cells induced by lipopolysaccharide (LPS) treatment and expression levels of inflammatory cytokine TNF-α, iNOS and IL-1β gene were analyzed using quantitative reverse transcription PCR (qRT-PCR) analysis. Results : The MTS assay was performed on RAW 264.7 cells after treatment with various concentrations of water extracts of SC. Treatment of RAW 264.7 cells with water extracts from SC and LPS at a concentration of 0.125, 0.5 mg/㎖ for twenty four hours promoted mRNA expression of TNF-α, iNOS and IL-1β. Conclusion : MTS assay was applied to RAW 264.7 cells after various concentrations of water extracts of SC. Through experimental demonstration of anti-oxidant and anti-inflammatory effects of water extracts from SC, we suggest that SC is a valuable material for the prevention and treatment of various inflammatory diseases.

• The Journal of Korean Medicine
• /
• v.30 no.4
• /
• pp.13-27
• /
• 2009

Objectives: Trans-cinnamaldehyde (TCA) is the main component of Cinnamomi Ramulus and it has been reported that TCA inhibits inflammatory responses in various cell types. Inflammation-mediated neurological disorders induce the activation of macrophages such as microglia in brain, and these activated macrophages release various inflammation-related molecules, which can be neurotoxic if overproduced. In this study, we evaluated gene expression profiles using gene chip microarrays in lipopolysaccharide (LPS)-stimulated BV-2 cells to investigate the antiinflammatory effect of TCA on inflammatory responses in brain microglia. Methods: A negative control group was cultured in normal medium and a positive control group was stimulated with $1{\mu}g/ml$ in the absence of TCA. TCA group was pretreated with $10{\mu}g/ml$ before $1{\mu}g/ml$ LPS stimulation. The oligonucleotide microarray analysis was performed to obtain the expression profiles of 28,853 genes using gene chip mouse gene 1.0 ST array in this study. Results: In positive control group, 1522 probe sets were up-regulated in the condition of the cutoff value of 1.5-fold change and 341 genes with Unigene ID were retrieved. In TCA group, 590 probe sets were down-regulated from among 1522 probe sets and 33 genes with Unigene ID were retrieved, which included 6 inflammation-related genes. We found out that Id3 gene is associated with transforming growth factor-${\beta}$ (TGF-${\beta}$) signaling pathway and Klra8 gene is related to natural killer cell-mediated cytotoxicity pathway. Conclusions: The results mean that TCA inhibits inflammatory responses through down-regulating the expressions of inflammation-related genes in LPS-stimulated BV-2 cells.

• The Korean Journal of Physiology and Pharmacology
• /
• v.24 no.5
• /
• pp.395-402
• /
• 2020

This study has investigated the effect of a potent bioflavonoid, troxerutin, on diabetes-induced changes in pro-inflammatory mediators and expression of microRNA-146a and nuclear factor-kappa-B (NF-κB) signaling pathway in aortic tissue of type-I diabetic rats. Male Wistar rats were randomly divided into four groups (n = 6/each): healthy, healthy-troxerutin, diabetic, and diabetic-troxerutin. Diabetes was induced by streptozotocin injection (60 mg/kg; intraperitoneally) and lasted 10 weeks. Troxerutin (150 mg/kg/day) was administered orally for last month of experiment. Inflammatory cytokines IL-1β, IL-6, and TNF-α, as well as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM), cyclooxygenase-II (COX-II), and inducible-nitric oxide synthase (iNOS) were measured on aortic samples by enzyme-linked immunosorbent assay. Gene expressions for transcription factor NF-κB, interleukin-1 receptor-associated kinase-1 (IRAK-1), TNF receptor-associated factor-6 (TRAF-6), and microRNA-146a were determined using real-time polymerase chain reaction. Ten-week diabetes significantly increased mRNA levels of IRAK-1, TRAF-6, NF-κB, and protein levels of cytokines IL-1β, IL-6, TNF-α, adhesion molecules ICAM-1, VCAM, and iNOS, COX-II, and decreased expression of microRNA-146a as compared with healthy rats (p < 0.05 to p < 0.01). However, one month treatment of diabetic rats with troxerutin restored glucose and insulin levels, significantly decreased expression of inflammatory genes and pro-inflammatory mediators and increased microRNA level in comparison to diabetic group (p < 0.05 to p < 0.01). In healthy rats, troxerutin had significant reducing effect only on NF-κB, TNF-α and COX-II levels (p < 0.05). Beside slight improvement of hyperglycemia, troxerutin prevented the activation of NF-κB-dependent inflammatory signaling in the aorta of diabetic rats, and this response may be regulated by microRNA-146a.

• Journal of Haehwa Medicine
• /
• v.22 no.1
• /
• pp.145-170
• /
• 2013

Objectives : This study was carried out to investigate the anti inflammatory and anti allergy effects of Vitex rotundifolia Linne fil. extract(VRE). Results : 1. In vitro test, VRE was used to determine the modulation of cytokine secretion, the activation of inflammatory and allergic factor and the inhibition of gene expression. The cell survival rate of Raw 264.7 and Jurkat T cells didn't decrease and accordingly cytotoxicity wasn't observed. In anti-allergic assay, the secretion of IL-2, TNF-${\alpha}$, IL-4, IL-5 and IFN-${\gamma}$ were suppressed on Jurkat T cells induced by dust mites. And the gene expression of COX-2 was suppressed in HMC-1 stimulated by calcium ionophore A23187. In anti-inflammatory assay, the gene expression of TNF-${\alpha}$, COX-2 were suppressed on LPS-activated Raw 264.7 cells. And the secretion of IL-6 and IL-8 were suppressed on EoL-1 cells induced by dust mites. P38 and ERK activation of MAPK decreased generally. VRE showed potent inhibitory activity of NO production. 2. In vivo test, we used NC/Nga mouse induced by atopic dermatitis to observe the effects of VRE on the weight, water and feed, blood test, weight of organs, total IgE and histological change of main organs. Quantity of water and feed were not changed, therefore it didn't affect the weight directly, and no change was observed in related main organs, thus maybe there is no organ toxicity by test substances. And the symptoms were decreased significantly, and the thickness of epithelial cell layer and the number of mast cells were inhibited significantly by the difference of dosage. The number of total complete blood cells and IgE in serum were not changed significantly. Conclusion : These results suggest that VRE has anti-inflammatory and anti-allergic effects. Therefore VRE could be used effectively on improvement or treatment of atopic dermatitis. However, further study is needed to prove which component of VRE indicates effective pharmacological action.