• Parasites, Hosts and Diseases
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• v.47 no.2
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• pp.145-151
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• 2009

This study examined the association of cytokine gene polymorph isms with intrahepatic bile duct wall fibrosis in human clonorchiasis. A total of 240 residents in Heilongjiang, China underwent ultrasonography, blood sampling, and stool examination. Single nucleotide polymorphism (SNP) sites for $IFN-{\gamma}$ (+874 T/A), IL-10 (-1,082 G/A, -819 C/T, -592 C/A), $TNF-{\alpha}$ (-308 G/A), and $TGF-{\beta}1$ (codon 10 T/C, codon 25 G/C) genes were observed with the TaqMan allelic discrimination assay. No significant correlation was observed between individual cytokine gene polymorphisms and intrahepatic duct dilatation (IHDD). Among individuals with clonorchiasis of moderate intensity, the incidence of IHDD was high in those with $IFN-{\gamma}$ intermediate-producing genotype, +874AT (80.0%, P=0.177), and in those with $TNF-{\alpha}$ low-producing genotype, -308GG (63.0%, P=0.148). According to the combination of $IFN-{\gamma}$ and $TNF-{\alpha}$ genotypes, the risks for IHDD could be stratified into high (intermediate-producing $IFN-{\gamma}$ and low producing $TNF-{\alpha}$), moderate, and low (low-producing $IFN-{\gamma}$ and high producing $TNF-{\alpha}$) risk groups. The incidence of IHDD was significantly different among these groups (P=0.022): 88.9% (odds ratio, OR=24.0) in high, 56.5% (OR=3.9) in moderate, and 25.0% (OR=1) in low risk groups. SNP of $IFN-{\gamma}$ and $TNF-{\alpha}$ genes may contribute to the modulation of fibrosis in the intrahepatic bile duct wall in clonorchiasis patients.

• Parasites, Hosts and Diseases
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• v.38 no.2
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• pp.85-90
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• 2000

To assess the relationship between the changes of cellular components and the production of Th 1 cytokine in the immune tissue, inbred C57BL/6 mice were orally infected with 40 cysts of 76K strain of Toxoplosma gondii. The sequential change of cell differentials and $IFN-{\gamma}$ production of splenocytes were analyzed by Diff-Quik stain and RT-PCR. There were no significant proportional changes of cellular components of splenocytes until day 4 postinfection (Pl) as compared to those of day 0, and the relative percentage of macrophages and neutrophils/eosinophils increased significantly (p<0.01) thereafter. The expression of $IFN-{\gamma}$ mRNA of $CD3^{-}$ cells was observed from day 1 Pl at a low level. However, $IFN-{\gamma}$ production of $CD3^{+}$ cells increased significantly from day 4 Pl (p<0.01) which progressively increased thereafter. These findings provide the relative percentages of granulocytes and macrophages were increased in conjunction with increase of total number of splenocytes after oral infection with T. gondii in the susceptible murine hosts, and lymphocytes were the major cellular components and the important source of $IFN-{\gamma}$.

• The Korean Journal of Food And Nutrition
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• v.20 no.3
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• pp.259-264
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• 2007

Ginger(Zingiber officinale Roscoe) has been used as a raw material in many various traditional preparations since the ancient times. As a component of traditional health products, ginger is known to be effective as an appetite enhancer, and has anti-cold and anti-inflammatory activities. This study was performed to investigate the immunomodulative effects of Zingiber officinale Roscoe in mice, using ex vivo experiments. In order to elucidate ginger's immunomodulative effects of Ginger, water extracts were orally administered to mice, and isolated macrophages were used as the experimental model. To identify the ex vivo effects, six to seven week old Balb/c mice were fed a chow diet ad libitum and the ginger water extracts were administered orally every other day for two or four weeks at two different concentrations(50 and 500 mg/kg b.w.). The results show that IL-IO and $IFN-{\gamma}$ were detected in the 500 mg/kg b.w. supplemented group with LPS stimulation in all cases. Also, the $IFN-{\gamma}$ /IL-10 ratio ranged from 3~5 with mitogen stimulation such as Con A and LPS. In conclusion, this study suggests that ginger extracts may enhance the immune function by regulating the cytokine(IL-10 and $IFN-{\gamma}$) production capacity of activated macrophages in mice.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.2
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• pp.422-426
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• 2008

In this study, the preventive effects of Radix Trichosanthis extracts (RTE) against cytokine-induced ${\beta}-cell$ death were assessed. Cytokines generated by immune cells infiltrating pancreatic islets are crucial mediators of ${\beta}-cell$ destruction in insulin-dependent diabetes mellitus. The treatment of RIN cells with $interleukin-1{\beta}$ ($IL-1{\beta}$) and $interferon-{\gamma}$ ($IFN-{\gamma}$) resulted in a reduction of cell viability. RTE protected $IL-1{\beta}$ and $IFN-{\gamma}$-mediated viability reduction in a concentration-dependent manner. Incubation with RTE also induced a significant suppression of $IL-1{\beta}$ and $IFN-{\gamma}$-induced inducible nitric oxide synthase (iNOS) protein expression. The molecular mechanism by which RTE inhibited iNOS protein expression appeared to involve the inhibition of $NF{-\kappa}B$ activation. The $IL-1{\beta}$ and $IFN-{\gamma}$-stimulated RIN cells showed increases in $NF{-\kappa}B$ binding activityand $I{\kappa}B{\alpha}$ degradation in cytosol compared to unstimulated cells. However, pretreatment with RTE inhibited cytokines-induced $I{\kappa}B{\alpha}$ degradation and $NF{-\kappa}B$ activation in RINm5F cells. Furthermore, the protective effects of RTE were verified via protection of impairment in glucose-stimulated insulin secretions in $IL-1{\beta}$ and $IFN-{\gamma}$-treated islets.

• Biomolecules & Therapeutics
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• v.18 no.2
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• pp.211-218
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• 2010

Acanthopanax koreanum Nakai (Araliaceae) is a medicinal plant indigenous to Korea. The root and stem barks of Acanthopanax species have been used as a tonic and sedative as well as in the treatment of rheumatism and diabetes. In our study, three lignans, eleutheroside E (EE), tortoside A (TA), and syringaresinol (SY), were isolated from the stem and root of A. koreanum in an effort to study the immunomodulating effect. We treated natural killer cells and dendritic cells with lignans (EE, TA, or SY), and analyzed their cytokine (IL-12 and IFN-${\gamma}$) secretion. EE, TA, or SY markedly enhanced IL-12 secretion in mouse lymphoid (DC1) and myeloid type (DC2.4) dendritic cells after 48 hr of treatment. There were no significant differences in the cytokine stimulatory effects between EE, TA, or SY. Moreover, treatment of EE, TA, or SY significantly induced IFN-${\gamma}$ secretion by human NK cells (NK92MI) confirmed by ELISA assay. This study suggests that lignans from A. koreanum modulate cytokines, and that such modulation may provide the mechanism of action for many of their therapeutic effects.

• The Journal of Internal Korean Medicine
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• v.25 no.2
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• pp.245-257
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• 2004

This study was done to evaluate the antiallergic effects of Naenghyohwan(NHH). Cytotoxic activity for lung fibroblast cells, cytokines transcript expression of IL-1, IL-4, IL-5, TNF-${\alpha}$, IL-6, IL-10, TGF-${\beta}$1, IFN-${\gamma}$, production of IL-4, IL-10. IFN-${\gamma}$, IgE in anti-CD40mAb plus rIL-4 stimulated murine splenic B cells and the production of histamin released in mast cells, and the expression of histamine release factor(HRF) in splenic B cells were measurd. The following results were obtained. NHH did not showed cytotoxicity in fibroblast cells. NHH increased the gene synthesis of TNF-${\alpha}$, IFN-${\gamma}$(m-RNA). NHH decreased the gene synthesis of IL-1${\beta}$, IL-4, IL-5, IL-6, TGF-${\beta}1$(m-RNA). NHH decreased the appearance of IL-4, IgE significantly. NHH increased the appearance of IL-10. IFN-${\gamma}$ significantly. NHH decreased the proliferation of B cells significantly. NHH decreased the appearance of histamin expression of HRF in mast cells significantly. The results suggest NHH is effective against the allergies. Continued studies of the antiallergic effects of NHH are urged.

• BMB Reports
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• v.34 no.6
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• pp.578-583
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• 2001

As a prototypic Thl vs Th2 cytokine, IFN-$\gamma$ and IL-4 activate distinct STAT proteins, STAT1 and STATE, respectively. In cytokine-producing Jurkat T cells, IL-4 is effectively rescued from cell death that is induced by dexamethasone, but IFN-$\gamma$ failed to do so. Since the Ras/MAPK pathway is known to play an important role in cytokine-induced cell survival, we investigated the mechanism of T cell survival through the analysis of functional cross-talk between Ras/MAPK and distinct STAT proteins that are activated by IL-4 and IFN-$\gamma$. Although IL-4 and IFN-$\gamma$ each induced the activation of STATE and STATI. in Jurkat T cells, respectively, only IL-4 was capable of inducing MAPK. Along with tyrosine kinase inhibitors, MEK/MAPK inhibitors also caused a significant suppression of the IL-4-induced STATE activity. This suggests a positive regulation of STATE by MAPK during IL-4 signal transduction. Furthermore, transfection studies with dominant active (da) vs dominant negative (dn) Ras revealed that daRas, but not dnRas, selectively up-regulated the expression and activity of STATE with a concomitant increase in MAPK activity. These results, therefore, suggest that there is a functional cross-talk between the Ras/MAPK and Jak/STAT6 pathways, which may have a role in the IL-4-induced T cell survival.

• Journal of Veterinary Clinics
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• v.20 no.4
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• pp.478-481
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• 2003

Canine juvenile cellulitis (CJC) is a well-recognized lymphocutaneous disease that is seen in young dogs. CJC seemed to be immunologic disorder and may have a hereditary aspect. Exact pathogenesis and cytokine regulation on the immune system of CJC are not clear. CJC was diagnosed in two puppies hospitalized in Veterinary Teaching Hospital of Chungbuk National University. To investigate the cytokine regulation on CJC, RT-PCR was performed with CJC affected dogs. RT-PCR 1 was performed with whole blood sample (CJC-B) and fine needle aspirates of the inguinal lymph node (CJC-LN) from case 1-dog, which included $TNF-\alpha,$ $IL-1\beta,$ $IFN-\gamma,$ IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 and $\beta-actin.$ Blood sample from a normal dog (N-B) served for a negative control of RT-PCR 1 (case 1). $IFN-\gamma,$ IL-2, IL-4, IL-5, IL-8, IL-10 and IL-12 transcripts were not expressed in all sample. $TNF-\alpha$ and $IL-1\beta,$ were not transcripted from CJC-B but from CJC-LN. On RT-PCR 2 (case 2), submandibular lymph node aspirates were used and $TNF-\alpha,$ IL-10, $IFN-\gamma$ and $IL-1\beta$ were expressed. $TNF-\alpha,$ 1L-10 and $IFN-\gamma$ were secreted from activated macrophages enhance the inflammation in tissue. These results imply that abnormally increased macrophages secret $TNF-\alpha$ and $IL-1\beta$ in the affected lymph nodes, which attract neutrophils and cause inflammation in CJC.

• Journal of Periodontal and Implant Science
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• v.30 no.4
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• pp.895-913
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• 2000

It is becoming increasingly clear that human gingival fibroblasts(HGF) may play a role in regulating immune responsiveness in inflammatory periodontal lesions. Stimulation of HGF with locally-secreted T cell cytokine $IFN_{\gamma}$ induces human leukocyte antigen class II(HLA II) expression on HGF, which is one of the characteristic feature of professional antigen presenting cells(pAPC). However, $IFN_{\gamma}$-treated HGF and other nonprofessional antigen presenting cells(npAPC) are known to be ineffective or less effective antigen presenter to resting T cells. This study, therefore, was undertaken in an effort to elucidate the differences in expression of cell surface molecules between npAPC in periodontal tissues, such as HGF and periodontal ligament fibroblasts(PDLF), and pAPC such as monocytes/macrophages. Using flow cytometry, the levels of cell surface expression of HLA-D, ICAM-1, LFA-3, and B7-1, which are involved in antigen presentation, were determined in HGF, PDLF and human myelomonocytic cell line THP-1. $IFN_{\gamma}$ clearly induced HLA-D expression on both of fibroblasts and monocytes dose dependently. However, expression level on monocytes were 4 to 5 times higher than that on fibroblasts, and induction rate was faster in monocytes than in fibroblasts. The levels of ICAM-1 expression on fibroblasts and monocytes were enhanced by $IFN_{\gamma}$ in a dose dependent manner. On the other hand, the expression of LFA-3 molecule, which could be detected in fibroblasts and monocytes without cytokine stimulation, was no more enhanced by addition of $IFN_{\gamma}$. B7-1, important costimulatory molecule in T cell activation and proliferation, was not detected on both of fibroblasts and monocytes even when stimulated with $IFN_{\gamma}$, except on monocytes fully differentiated by pretreatment of PMA and treated by $IFN_{\gamma}$. These results suggest that delayed expression of HLA-D and absence of B7-1 on $IFN_{\gamma}$ - treated fibroblasts may at least in part be involved in the ineffectiveness of fibroblasts as primary APC. And it is postulated that although periodontal fibroblasts may not serve as primary APC in normal periodontium, sustained expression of HLA II on ubiquitous fibroblasts in inflammatory lesions may perpetuate immune responses and produce chronic inflammation and tissue injury.

• Journal of Haehwa Medicine
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• v.10 no.2
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• pp.179-188
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• 2002

This experimental study was carried out to evaluate the effects of Acanthopanacis cortex on Cytokine-inducing and and immune response in Mice. In order to investigate the effect of Acanthopanacis cortex, the following was performed; Cytotoxicity, in vitro, the fraction of $CD4^+$, $CD8^+$, $B220^+$ in splenic cell, gene expression of IL-12(p35), IL-12(p40), IFN-${\gamma}$, and splenic cell proliferation by Acanthopanacis cortex. Analysis of cytokine gene expression was carried out by RT-PCR amplification. Amplified PCR products were electrophoresed on 1.2% agarose gel, and the analysis (Ht) was used to 1D-density program. The results were obtained as follows. Acanthpanacis cortex showed didn't have cell toxicity under $12{\mu}g/m{\ell}$ group on mouse lung fibroblast cells. In an in vitro model using mouse peripheral blood mononuclear cells (PBMCs), extract of Acanthpanacis cortex induced multiple cytokine, including interleukin-12 (p35), interleukin-12 (p40), interferon-gamma (IFN-${\gamma}$). The extract also enhanced the percentages of the $CD4^+$, and $CD8^+$ in the untreated control were $22.1{\pm}3.3$ to $38.4{\pm}2.1$, and $5.0{\pm}0.4$ to $10.7{\pm}0.3%$, respectively. From above findings, it is suggested that Acanthopanacis cortex is able to anti-cancer and activate immune response system.