• IMMUNE NETWORK
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• v.6 no.1
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• pp.20-26
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• 2006

Background: Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease that is characterized by invasive synovial hyperplasia, leading to progressive joint destruction. Recent studies have described that RA is caused by virus, bacteria or outside material. Approximately 2 to 20% of RA cases arc reported to be associated with infected hepatitis C virus (HCV). However, the mechanisms underlying virus-induced RA are still unknown. Moreover, few molecular studies have addressed the inflammatory aspects of HCV-associated autoimmune RA. In this study, we aimed to determine whe ther or not another HCV core protein transactivates the IL-8 gene expression, prototypic chemokine, in synovial cell. Methods: To establish the HCV core expressing stable synovial cell line, pCI-neo-core, a plasmid encoding HCV core protein, were transfected to HIG-82 cell line that is an established cell line from rabbit periaricular soft tissue. We examined the morphological changes and cell cycle distribution of HIG-82 cells with expression of HCV core protein by inverted microscopy and flow cytometry analysis, respectively. Also, we determined the mRNA levels of Interleukin (IL)-6 and IL-8 related to the inflammation by RT-PCR and then analyzed regulation of IL-8 expression by the NF-${\kappa}B$ pathway. Results: Our study showed no significant differences in morphology and cell cycle between HIG-82 control cell line and HIG-82 expressing HCV core protein. However, expression of HCV core protein induces the IL-8 mRNA expression in HIG-82 core cells via activated NF-${\kappa}B$ pathway. Conclusion: These results suggest that HCV core protein can lead to enhanced IL-8 expression. Such a proinflammatory role may contribute to the etiologic pathogenesis in RA patients with HCV infection.

• Korean Journal of Veterinary Research
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• v.50 no.2
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• pp.79-84
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• 2010

The molecule possessing ankyrin-repeats induced by lipopolysaccharide (MAIL) protein is a novel member of the $Ikappa{\beta}$ family. In the present study, we examined the effect of norepinephrine (NE) on MAIL mRNA expression in primary cultured mouse hepatocytes and non-parenchymal liver cells. MAIL mRNA expression in hepatocytes and non-parenchymal liver cells was not directly influenced by NE. However, MAIL mRNA expression in hepatocytes was significantly induced by incubation with a culture medium of non-parenchymal liver cells, treated with NE. Pretreatment with an interleukin (IL)-1 receptor antagonist significantly attenuated the stimulatory effect of the medium. Moreover, exogenous $IL-1{\beta}$ induced MAIL mRNA expression in hepatocytes, while IL-6 and tumor necrosis factor $\alpha$ did not. The concentration of $IL-1{\beta}$ in the medium of non-parenchymal liver cells was significantly increased after NE-treatment. These results suggest that NE can induce MAIL mRNA expression in hepatocytes through $IL-1{\beta}$, released from non-parenchymal liver cells.

• Annals of dermatology
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• v.30 no.6
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• pp.645-652
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• 2018

Background: Adiponectin, an adipokine secreted from adipocytes, affects energy metabolism and also shows anti-diabetic and anti-inflammatory properties. Recent studies have reported that adiponectin plays a role in regulating skin inflammation. Objective: This study aimed to investigate the effect of adiponectin on the expression of filaggrin (FLG) in normal human epidermal keratinocytes (NHEKs). Methods: NHEKs were serum-starved for 6h before being treated with adiponectin. Afterward, cell viability was assessed by MTT assay. We also treated with calcium, interleukin (IL)-4, and IL-13 to provide positive and negative comparative controls, respectively. Gene mRNA expression was quantified using real time reverse transcription polymerase chain reaction, and protein expression was evaluated using Western blot. To evaluate the relationship among mitogen-activated protein kinases (MAPKs), activator protein 1 (AP-1), and FLG, we also treated cells with inhibitors for MAPKs JNK, p38, and ERK1/2. Results: FLG and FLG-2 mRNA expression in NHEKs significantly increased after treatment with $10{\mu}g/ml$ adiponectin. Adiponectin also restored FLG and FLG-2 mRNA expression that was otherwise inhibited by treatment with IL-4 and IL-13. Adiponectin induced FLG expression via AP-1 and MAPK signaling. Conclusion: Adiponectin positively regulated the expression of FLG and could be useful as a therapeutic agent to control diseases related to disrupted skin barrier function.

• Parasites, Hosts and Diseases
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• v.47 no.2
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• pp.117-124
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• 2009

Toxoplasma gondii provokes rapid and sustained nuclear translocation of the signal transducer and activator of transcription 6 (STAT6) in HeLa cells. We observed activation of STAT6 as early as 2hr after infection with T. gondii by the nuclear translocation of fluorescence expressed from exogenously transfected pDsRed2-STAT6 plasmid and by the detection of phosphotyrosine-STAT6 in Western blot. STAT6 activation occurred only by infection with live tachyzoites but not by co-culture with killed tachyzoites or soluble T. gondii extracts. STAT6 phosphorylation was inhibited by small interfering RNA of STAT6 (siSTAT6). In view of the fact that STAT6 is a central mediator of IL-4 induced gene expression, activation of STAT6 by T. gondii infection resembles that infected host cells has been stimulated by IL-4 treatment. STAT1 was affected to increase the transcription and expression by the treatment of siSTAT6. STAT6 activation was not affected by any excess SOCS's whereas that with IL-4 was inhibited by SOCS-1 and SOCS-3. T. gondii infection induced Eotaxin-3 gene expression which was reduced by $IFN-{\gamma}$. These results demonstrate that T. gondii exploits host STAT6 to take away various harmful reactions by $IFN-{\gamma}$. This shows, for the first time, IL-4-like action by T. gondii infection modulates microbicidal action by $IFN-{\gamma}$ in infected cells.

• The Journal of Korean Medicine
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• v.25 no.2
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• pp.51-66
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• 2004

Objectives : To evaluate experimentally the clinical effect of Bojeongjeongcheon-tang, we observed the cytokines ($IL-1{\beta}$/TEX>, IL-4, IL-5, IL-6, IL-10, TNF-{\alpha},{\;}TGF-{\beta},{\;}IFN-{\gamma}$) and what effect they have on IgE in B cells of a rat. Methods : First of all, we extracted the spleens of healthy Balb/c mice and separated B cells from them. These B cells were cultured with anti-CD40 mAb (500 ng/ml), rmIL-4 (500 U/ml), Bojeongjeongcheon-tang (100 ug/ml, 10 ug/ml, 1 ug/ml). We used rmiL-10 (50 ng/ml) as a control group. Furthermore, we analyzed the expression of IgE, CD23, CD69 and the coherence of HRF in B cells using a flow cytometer. We also analyzed the cytokine gene expression in B cells by reverse transcriptase-PCR. We also measured B cells proliferation using the Liquid Scintillation Counter. Results : In this study, the Bojeongjeongcheon-tang treated group showed a tendency to decrease depending on the density compared with the control group in the expression of IgE+, CD23+, CD69, HRF. All of the Bojeongjeongcheon-tang treated group showed inhibitory effects with $IL-1{\beta}$, IL-4, IL-5 and proliferating effects with IL-6, IL-10, and $IFN-{\gamma}$ on cytokines transcript expression depending on the density. Meanwhile, $TNF-{\alpha}$ increased in all density. In IgE production, there was inhibitory effect on Bojeongjeongcheon-tang (both 100 ug/ml and 10 ug/ml) of significance (p < 0.01, p < 0.05). Also in B cell proliferation, the result revealed an inhibitory effect of Bojeongjeongcheon-tang (both 100 ug/ml and 10 ug/ml), of significance (p < 0.001, p < 0.01). Conclusions : This study shows that Bojeongjeongcheon-tang has an inhibitory effect on the production and activity of B cells. Also it inhibited CD23, IL-4 activity and IgE production and activation. It is obvious that Bojeongjeongcheon-tang treats asthma by inhibiting the production of histamine and HRF, IL-5 and proliferating IL-10. Also Bojeongjeongcheon-tang has some preventive effects on bronchial change by inhibiting $TGF-{\beta}$, which stimulates the bronchial transformation.

• The Korea Journal of Herbology
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• v.28 no.1
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• pp.33-42
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• 2013

Objective : Morus alba Linne Root Bark (MRAL) is a medicinal herb in Korean Medicine, known for its anti-inflammatory and anti-allergic properties. However, its mechanisms of action and the cellular targets have not yet been found and the study was developed to investigate the allergic suppressive effect of MRAL. The purpose of this study is to investigate the allergic suppressive effects of MRAL on activation of MC/9 mast cells. Methods : Cytotoxic activity of MRAL (50, 100, 200, 400 ${\mu}g/mL$) on MC/9 mast cells measured using EZ-Cytox cell viability assay kit (WST reagent). The levels of interleukin-5 (IL-5), IL-13 and IL-4, IL-5, IL-6, IL-13 mRNA expression were measured by enzyme-linked immunosorbent assay (ELISA) and real-time PCR respectively. The expression of transcription factors such as GATA-1, GATA-2, NFAT, AP-1 and NF-${\kappa}B$ p65 DNA binding activity were measured by western blot and electrophoresis mobility shift assay (EMSA). Results : Our results indicated that MRAL (50 ${\mu}g/mL$, 100 ${\mu}g/mL$) significantly inhibited PMA/Ionomycin-induced production of IL-5 and IL-13 and the expression of IL-4, IL-5, IL-6 and IL-13 mRNA in MC/9 mast cells. Moreover, MRAL (50 ${\mu}g/mL$, 100 ${\mu}g/mL$) inhibited PMA/Ionomycin-induced GATA-1, GATA-2, NFAT-1, NFAT-2, c-Fos protein expression and NF-${\kappa}B$ p65 DNA binding activity in MC/9 mast cells. Conclusions : In conclusion, we suspect the anti-allergenic activities of MRAL, may be related to the regulation of transcription factors GATA-1, GATA-2, NFAT-1, NFAT-2, c-Fos and NF-${\kappa}B$ p65 DNA binding assay causing inhibition of Th2 cytokines IL-5 and IL-13 in mast cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.6
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• pp.1869-1880
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• 2004

In the oriental medicine, a mixture of herbs has been commonly used as important components to control allergic and inflammatory diseases. In the present study, we prepared a mixture of Dictamni Radicis Cortex(Baiksunpee), Houttuyniae Herba(Uhsungcho), and Aurantii Immaturus Fructus(Jisil) to examine its anti-allergic effects in activated mouse splenic cells and found that Mix-1 is involved in regulating levels of B cell activating factors (CD23 and CD11a), IL-1β, IL-6, IL-10, TNF-α, and 1gE as well as HRF expression. It was observed that Mix-1 did not have cytotoxic effects on mLFC. Mix-1 showed inhibition of CD23 and CD11 alpaha expression in mouse B cells, and also decreased the production of IL-6, TNF-α, and 1gE. Both RT-PCR and ELISA analyses indicated that IL-6 and TNF alpha production were regulated at the gene expression level. In contrast, IL-10 mRNA and protein levels were increased in activated B cells by Mix-1 treatment. We also found that Mix-1 inhibited B cell proliferation and inhibited histamine releasing factor(HRF) expression, suggesting its inhibitory effect on histamine secretion. These data indicated that Mix-1 has an anti-allergic effect in activated macrophages and further suggest the possible application of Mix-1 as a therapeutic agent for the treatment of allergy-related diseases.

• Food Science of Animal Resources
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• v.43 no.1
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• pp.101-112
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• 2023

This study aimed to assess whether genomic DNA (gDNA) extracted from Pediococcus acidilactici inhibits Porphyromonas gingivalis lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 cells. Pretreatment with gDNA of P. acidilactici K10 or P. acidilactici HW01 for 15 h effectively inhibited P. gingivalis LPS-induced mRNA expression of interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein (MCP)-1. Although both gDNAs did not dose-dependently inhibit P. gingivalis LPS-induced mRNA expression of IL-6 and MCP-1, they inhibited IL-1β mRNA expression in a dose-dependent manner. Moreover, pretreatment with both gDNAs inhibited the secretion of IL-1β, IL-6, and MCP-1. When RAW 264.7 cells were stimulated with P. gingivalis LPS alone, the phosphorylation of mitogen-activated protein kinases (MAPKs) was increased. However, the phosphorylation of MAPKs was reduced in the presence of gDNAs. Furthermore, both gDNAs restored IκBα degradation induced by P. gingivalis LPS, indicating that both gDNAs suppressed the activation of nuclear factor-κB (NF-κB). In summary, P. acidilactici gDNA could inhibit P. gingivalis LPS-induced inflammatory responses through the suppression of MAPKs and NF-κB, suggesting that P. acidilactici gDNA could be effective in preventing periodontitis.

• Journal of Ginseng Research
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• v.22 no.4
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• pp.324-330
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• 1998

We Previously reported that Polysaccharide Isolated from panax ginseng C. A. Meyer, stimulates murine splenocytes to proliferate and to be cytotoxic against a wide range of tumor cells in MHC non-restricted manner:) Therefore, we examined the cytokine mRNA expression induced by the ginseng polysaccharide in this paper. This study demonstrates that the ginseng polysaccharide stimulates Thl type cytosine expression such as IL-2 and IFNY, and macrophage type cytokine expression such as IL-lc and GM-CSF in a dose-dependent manner at different time: IL-2 mRNA was induced at 30 min, IL-la, GM-CSF mRNA at 3 hr, IFNY at 6 hr after the ginseng polysaccharide treatment. In contrast with these, Th2 type cytokine expression such as IL-4 and IL-5 was not induced. The generation of the ginseng polysaccharide-activated killer cells which was induced at the optimal doses of 50 pEyml was neutralized in the presence of anti-lL-2, anti-lFNy, anti-IL-l ${\alpha}$ antibodies, showing the importance of these cytokines produced by the ginseng polysaccharide. In flow cytometry analysis, the blastogenesis of IgM+ cells was induced on day 3 and the number of Thy 1.21 cells, CD4+ and CD8+ cells was increased on day 5. The ginseng polysaccharide also induced blastogenesis of T cells. In conclusion, the ginseng polysaccharide may have considerable antitumor immunotherapeutic modality by stimulating the cytokine production from Thl cells and macrophage and by proliferating lymphocytes.

• Biomedical Science Letters
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• v.18 no.1
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• pp.56-62
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• 2012

This study was to investigate the effects of high-fat diet feeding for a very long period of time on gene expression of inflammatory cytokines in mouse adipose tissue and to determine whether caloric restriction (CR) or insulin sensitizer treatment changes the cytokine gene expressions even in obese mice fed a high-fat diet for a very long term-period. Gene expression levels of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) were examined by real-time PCR in subcutaneous abdominal adipose tissue (SubQ) from obese and non-obese male C57BL/6 mice at 16, 26, 36, 47, and 77 weeks of age on either normal diet (ND) or high-fat diet (HFD) after starting at 6 weeks of age. In addition, gene expression levels of TNF-${\alpha}$, IL-6 and MCP-1 were determined in SubQ before and after rosiglitazone treatment or CR on 47-week-old obese mice. The results demonstrated that gene expression levels of TNF-${\alpha}$, IL-6 and MCP-1 were significantly increased with aging in SubQ of mice in both groups of diet. MCP-1 gene expression of SubQ in all ages tested was significantly or marginally increased in mice on HFD compared with ND. While TNF-${\alpha}$ expression was significantly reduced by rosiglitazone, IL-6 and MCP-1 were significantly decreased by CR. The basic data in this study will be useful for characterizing the C57BL/6 mouse as an animal model of obesity induced by high-fat diet feeding for a very long period of time, and a better understanding of inflammatory cytokine regulation in diet induced obesity which may facilitate the development of new therapeutic strategies to prevent the complications of obesity.