• IMMUNE NETWORK
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• v.3 no.1
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• pp.8-15
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• 2003

Background: CD30 is a member of TNF receptor family and expressed on lymphocytes and other hematopoietic cells following activation as well as Hodgkin and Reed-Sternberg cells in Hodgkin's lymphoma. In this study, CD30-mediated regulation of cell adhesion molecule expression on normal activated mouse T cells was investigated. Methods: Mouse T cells were activated with anti-CD3 antibody for induction of CD30, which was cross-linked by immobilized anti-CD30 antibody. Results: High level of CD30 expression on T cells was observed on day 5, but only little on day 3 even under culture condition resulting in an identical T cell proliferation, indicating that CD30 expression requires a prolonged stimulation up to 5 days. Cross-linking of CD30 alone altered neither proliferation nor apoptosis of normal activated T cells. Instead, CD30 appeared to promote cell adherence to culture substrate, and considerably upregulated ICAM-1 and, to a lesser extent, ICAM-2 expression on activated T cells, whereas CD2 and CD18 (LFA-1) expression was not affected. None of cytokines known as main regulators of ICAM-1 expression on tissue cells (IL 4, $IFN{\gamma}$ and $IFN{\alpha}$) enhanced ICAM-1 expression in the absence of CD30 signals. On the other hand, addition of $NF-{\kappa}B$ inhibitor, PDTC (0.1 mM) completely abrogated the CD30-mediated upregulation of ICAM-1 expression, but not CD2 and ICAM-2 expression. Conclusion: This results support that CD30 upregulates ICAM-1 expression of T cell and such regulation is not mediated by higher cytokine production but $NF-{\kappa}B$ activation. Therefore, CD30 may play important roles in T-T or T-B cell interaction through regulation of ICAM-1, and -2 expression.

• IMMUNE NETWORK
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• v.3 no.1
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• pp.61-68
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• 2003

Background: Fibroblast functions both as a structural element and as a vital immunoregulatory cell. Fibroblasts regulate inflammation through governing of chemokine expression. In order to elucidate the mechanisms by which the expressions of chemokines were regulated, the co-stimulatory effects of Th1 and proinflammatory cytokines were compared using nasal mucosal fibroblasts. Methods: Human nasal mucosa was obtained from surgery for septal deviation and the growth of fibroblasts was established. Fibroblasts from 4th to 6th passage were stimulated with various combinations of cytokines. To inhibit selected signaling pathways, fibroblasts were pretreated with cyclosporin A, wortmannin, staurosporine, and dexamethasone prior to the stimulation with cytokines. The supernatants were collected and chemokines were detected with a sandwich enzyme-linked immunosorbent assay. Results: $TNF-{\alpha}/IFN-{\gamma}$-induced production of RANTES was inhibited by all inhibitors used. MCP-1 was produced constitutively and $TNF-{\alpha}$-induced or $TNF-{\alpha}/IFN-{\gamma}$-induced production of MCP-1 was not inhibited by cyclosporin A or wortmannin, but by stauroporine or dexamethasone. All inhibitors used in this experiment inhibited $TNF-{\alpha}/IFN-{\gamma}$-induced or $IL-1{\beta}/IFN-{\gamma}$-induced production of MCP-2 in nasal mucosal fibroblasts. Although staurosporine or dexamethasone showed strong inhibitory effects, cyclosporin A or wortmannin did not inhibit the production of MCP-3 by $IL-1{\beta}/IFN-{\gamma}$ treatment. Conclusion: Chemokines were strongly induced by stimulation of cytokines in combination and showed different pattern of inhibition by the inhibitors. Therefore, it was assumed that cytokines acted on multiple pathways or on unknown pathways which converged to gene-specific transcription factors.

• Asian-Australasian Journal of Animal Sciences
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• v.24 no.7
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• pp.889-897
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• 2011

Mycoplasma Pneumonia of swine (MPS) decreases the daily growth of pigs, and, co-infection with a virus sometimes causes severe pneumonia. Genetic selection of pigs resistant to the pulmonary MPS lesion might solve the economic loss due to MPS in animal production. Here, we examined the immunophenotype of Landrace line (Miyagino L2), genetically selected to reduce the incidence of pulmonary MPS lesion for 5 generations in Miyagi Prefecture Animal Industry Experiment Station. Although this line is expected to be resistant to the pulmonary MPS lesion, the biological characteristics of its immune function are not clear. We investigated details of the immunorelated phenotype of Miyagino L2 at the hematological and molecular biological level, including cytokine expression, and compared the results with that of non-genetically selected Landrace. Miyagino L2 showed decreased antigen-specific IgG and IgM production and increased CD8-positive T-cell population, and high levels of cortisol concentration, suggesting that the MPS-resistant phenotype is associated these immunological differences. Additionally, T-cell CD4 expression was highly correlated with the MPS expected breeding value. Although the detailed mechanisms underlying this high correlation remain unknown, our result suggested that the genetic selection of the expression level of CD4 might be useful to improve MPS resistance in pig production.

• Preventive Nutrition and Food Science
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• v.8 no.3
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• pp.253-259
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• 2003

Conjugated linoleic acid (CLA) is a class of positional, geometric conjugated dienoic isomers of linoleic acid (LA). CLA activates the immune system, protects against tumorigenesis, and reduces the incidence of atherosclerosis. Trans-10, cis-12 CLA has specific effects on lipid metabolism, it has been shown to reduce body fat gain and regulates some adipocyte secreted proteins in vivo and in vitro. Here we report that a CLA mixture affects cytokine secretion from rat primary adipocytes. Rat primary adipocytes were treated with 1 mM, 100 $\mu$M, 1 $\mu$M or 100 nM CLA mixture doses; and leptin, tumor necrosis factor alpha (TNF a ), interleukin-6 (IL-6) and glycerol levels in the medium were measured. Leptin secretion was lower, TNF $\alpha$ secretion higher and IL-6 secretion did not change in response to the CLA mixture. Leptin and TNF $\alpha$ secretions did not change with CLA mixture treatment in a dose-dependent manner. In addition, the CLA mixture did not appear to enhance lipolysis in rat primary adipocytes. In conclusion, our study demonstrates that the decrease in leptin and increase in TNF $\alpha$ secretion in adipocytes treated with CLA mixture may be due to the apoptotic effect and to a reduction in peroxisome proliferator-activated receptor gamma (PPAR ${\gamma}$ ) ligands.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.1061-1070
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• 2004

Chronic oral aphthae, recurrent ulcer and uveitis are the three main festations of Behcet's disease(BD). The aetiopathogenesis of Behcet's disease is still obscure, but herpes simplex virus is one of the possible casual factors. Gamchosasim-tang (Gancaoxiexin-tang), Banhasasim-tang(Banxiaxiexin-tang) and Saenggangsasim-tang( Shengjiangxiexin-tang) are traditional medication in Oriental medicine, that has been used to treat inflammatory disease. Especially, Gamchosasim-tang used to treat Behcet's disease like symptoms. ICR mice were used for this study. The earlobe of the mice were scratched with a needle, then inoculation with 1.0×10/sup 6/ plaque forming units/㎖ of HSV type I. Virus inoculation was performed twice with 10 day interval, followed by 16 weeks of observation. Using the HSV-induced Behcet's disease mouse model, kinds of Sasim-tang were administered variously before and after inoculation. In order to. classify the symptomatic mice as having Behcet's disease like symptoms. We followed the revised Japanese classification with minor modifications. Ulceration of the mice were monitored. In addition, spleen cytokine expression were measured by polymerase chain reaction, ELISA. HSV DNA was detected in HSV inoculation mice. HSV-induced mice treated with kinds of Sasim-tang showed improvement in symptom. In RT-PCR results, IFN-γ was expressed for all groups, IL-2 was expressed for the treated groups, and IL-10 was also expressed. IL-4 was expressed nothing. In ELISA, IL-2 was increased for GSST 2, BSST 2, GSST 2, GSST3 and INF-γ was increased for GSST 2, BSST 2, SSST 2, SSST 3. This model suggest the possible role of immune response to viral infection in the development and activation of Behcet's disease.

• Biomolecules & Therapeutics
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• v.26 no.6
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• pp.576-583
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• 2018

Human rhinoviruses (HRV) are one of the major causes of common cold in humans and are also associated with acute asthma and bronchial illness. Heat-shock protein 90 (Hsp90), a molecular chaperone, is an important host factor for the replication of single-strand RNA viruses. In the current study, we examined the effect of the Hsp90 inhibitor pochonin D, in vitro and in vivo, using a murine model of human rhinovirus type 1B (HRV1B) infection. Our data suggested that Hsp90 inhibition significantly reduced the inflammatory cytokine production and lung damage caused by HRV1B infection. The viral titer was significantly lowered in HRV1B-infected lungs and in Hela cells upon treatment with pochonin D. Infiltration of innate immune cells including granulocytes and monocytes was also reduced in the bronchoalveolar lavage (BAL) by pochonin D treatment after HRV1B infection. Histological analysis of the lung and respiratory tract showed that pochonin D protected the mice from HRV1B infection. Collectively, our results suggest that the Hsp90 inhibitor, pochonin D, could be an attractive antiviral therapeutic for treating HRV infection.

• Korean Journal of Veterinary Research
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• v.52 no.4
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• pp.231-238
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• 2012

The expression profiles of inflammatory cytokines viz. interleukins (IL)-6, IL-8, IL-12, granulocyte macrophage-colony stimulating factor, interferon-${\gamma}$ and tumor necrosis factor-${\alpha}$ in response to subclinical mastitis in indigenous cattle breed Kankrej (n = 6), Gir (Bos indicus) (n = 12) and crossbred (Bos taurus${\times}$Bos indicus) (n = 7) were investigated using quantitative real time PCR. Significant correlation (p < 0.05) was observed between total bacterial load and somatic cell count (SCC) in all three breeds of cattle. All the cytokines were observed to be up-regulated compared to cows with healthy quarters, however, level of their expression varied among three breeds of cattle. In Kankrej most cytokines were found to be transcribed to higher levels than in other two breeds; the milk had higher load of bacteria but not so high SCC, implying that Kankrej has a higher inherent resistance against mastitis. The results of present study indicated that mammary glands of crossbred cattle are more sensitive to bacterial infection than indigenous breed of cattle as they elicit immune response at lower bacterial load and result into higher SCC. Research on identification of factors responsible for differentially expressed cytokines profiles and use of cytokines as immunomodulatory tools can pave way for formulating control strategies against bovine mastitis.

• Journal of Applied Biological Chemistry
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• v.53 no.3
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• pp.139-146
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• 2010

The inhibitory effects of 25 polyphenols against in vitro allergic reactions were compared using biochemical and cell assays. Three polyphenols including curcumin, gallic acid, and quercetin suppressed the release of $\beta$-hexosaminidase from ionophore A23187-stimulated RBL-2H3 cells more effectively (>50% inhibition at $100{\mu}M$ concentration). They were found to have potencies in suppressing the release of histamine not only from ionophore A23187-, but also from immunoglobulin E (IgE)-stimulated RBL-2H3 cells. Moreover, such suppressive effects of the three polyphenols were also observed in A23187 plus PMA-costimulated rat peritoneal mast cells. The extent of inhibition were quantified as the respective polyphenol concentration that inhibit 50% ($IC_{50}$) of $\beta$-hexosaminidase or histamine release, showing an inhibition tendency with decreasing order of curcumin>gallic acid>quercetin. Down-regulation of $Ca^{2+}$ influx was suggested as the cause of the inhibition of $\beta$-hexosaminidase and histamine releases in these cells. The immune process inhibition was confirmed by the observed reduction in the gene expressions and release of pro-inflammatory cytokine tumor necrosis factor (TNF)-$\alpha$, interleukin (IL)-$1\beta$, and IL-4, due probably to antioxidant activity of the polyphenols. These findings illustrate that curcumin, gallic acid, and quercetin may be beneficial against allergic inflammatory diseases.

• The Journal of Korean Medicine
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• v.27 no.4
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• pp.30-47
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• 2006

Objective : The present study is aimed to elucidate the effects of Cirsium japonicum var. ussuriense on immunomodulation and the potential as an herbal remedy for cancer treatment. Method : It was performed through measurement of effects Cirsium japonicum var. ussuriense extract (CJE) on NO production, NK cell cytotoxicity and cytokine gene expressions related with macrophage and NK cell activity. Result : 1. CJE did not show any direct cytotoxic effects on 7250, HT1080, Hep G2 and CT-26 cells. 2. CJE activated macrophages partially to product NO and up-regulated gene expressions for iNOS in RAW 264.7 cells. 3. CJE promoted cytotoxicity of NK cells against YAC-1 cells at higher concentration than 200 ${\mu}g/ml$. 4. CJE up-regulated gene expressions for $IL-1{\beta}$, IL-2, iNOS, $IFN-{\gamma}$ and $TNF-{\alpha}$ in mice splenocytes.　５. CJE inhibited lung tumor metastasis induced by CT-26 cell transplantation compared with the control group.　Conclusion : It could be concluded that CJE is an effective herbal drug for immune modulating and anti-cancer treatment by promoting activity of macrophages and NK cells.

• The Journal of Korean Medicine
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• v.27 no.4
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• pp.182-190
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• 2006

Objective : Based on immunological mechanisms, this study examined whether subcutaneous (s.c.) injection of Clematis mandshurica Maxim. water extract (CMA) has anti-inflammatory effects, and its effect on $TNF-{\alpha}$, IL-1 and IL-10 release from synoviocytes on adjuvant arthritis (AA) in the rat. Methods : Complete Freund's adjuvant was used to induce AA in rats. Synoviocytes were separated by the method of collagenase and DNase digestion Synoviocytes proliferation was assayed by 3-(4, 5 dimethylthiazol 2 yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. $TNF-{\alpha}$, IL-1 and interleukin-10 (IL-10) production of synoviocytes was measured with ELISA. The expression of IL-10 mRNA of synoviocytes was determined using RT PCR. Results : There were significant secondary inflammatory reactions in AA rats, accompanied by the decrease of body and immune organs weight simultaneously. Synoviocytes proliferation of AA rats significantly increased, and the levels of $TNF-{\alpha}$ and IL-1 in supernatants of synoviocytes in AA rats were also elevated compared with the sham group. The administration of CMA (2, 5, 10 mg/kg, s.c.) reduced the above changes significantly. In contrast to $TNF-{\alpha}$ and IL-1, IL-10 production and the level of its mRNA of synoviocytes in AA rats apparently decreased. CMA (2, 5, 10 mg/kg, s.c.) markedly increased IL-10 in synoviocytes at protein and transcription level. Conclusion : The results indicate that CMA has a beneficial effect on rat AA due to modulating inflammatory cytokine production of synoviocytes, which play a crucial role in the pathogenesis of this disease.