• Food Science and Preservation
• /
• v.12 no.2
• /
• pp.173-178
• /
• 2005

Antitumor activities of methanol extract from onion Kochujang (MEOK) were investigated by using aflatoxin $B_{1}-mediated$ Salmonella typhimurium mutagenicity and the model of cytotoxicity on the cancer cell lines. Their immune activities were also investigated using mouse spleen cells and macrophage cell lines, respectively. MEOK showed the enhanced antimutagenicity in a dose-dependent manner. relative to the control group. MEOK decreased over $20\%$ of the proliferation of the A549(lung cancer cell) and MCF(breast cancer cell) cell lines at $1,000\;{\mu}g/mL$ concentration compared with the control cells. The proliferation of mouse spleen cells and the NO production in marcrophage cell lines treated MEOK were increased in a dose-dependent manner, respectively. The activities were higher than that of the control(no added onion) Kochujang.

• Journal of Life Science
• /
• v.23 no.10
• /
• pp.1199-1208
• /
• 2013

Fibroblastic reticular cells (FRCs) form the structural backbone of the T zone provide a guidance path for immigrating T cells in the lymph node (LN). FRCs may contribute directly to developing T-cell biology in the LN and allow analyses of fundamental aspects of FRC biology related to T cells. FRCs inhibited T-cell apoptosis, and FRC culture supernatants strongly induced the expression of Bcl-xL in T cells against doxorubicin. Coculture of FRC and T cells resulted in rearrangements of the actin cytoskeleton, as well as global changes in the morphology of the FRCs. In addition, when cocultured, the T cells adhered to the FRC monolayer, and the membrane intercellular adhesion molecule (ICAM)-1 was slightly increased by day-dependent manner. In contrast, the expression of soluble ICAM-1 was dramatically increased in a day-dependent manner. Several chemokines, such as CCL5, CXCL1, CXCL5, CXCL16, CCL8, CXCL13, and ICAM-1, and MMPs were expressed in FRCs sensed by tumor necrosis factor (TNF) families. Nuclear factor kappa B ($NF{\kappa}B$)-RelA of the $NF{\kappa}B$ canonical pathway was translocated into FRC nuclear by $TNF{\alpha}$. In contrast, p52 proteolyzed from p100, a counterpart of RelB of the noncanonical $NF{\kappa}B$ pathway, accumulated in the peripheral FRC nucleus by agonistic anti-$LT{\beta}R$ antibody. In summary, we propose a model in which FRCs engage in bidirectional crosstalk to increase the efficiency of T-cell biology. This cooperative feedback loop may help to maintain tissue integrity and function during immune responses.

• The Journal of Pediatrics of Korean Medicine
• /
• v.24 no.1
• /
• pp.9-35
• /
• 2010

Objectives The purpose of this study is to investigate the effect of SPDJTK(SoPungDoJeokTangKami) and concurrent administration of AJ(Atopy cream, Jawoongo)+SPDJTK on atopic dermatitis-like skin lesions by using in NC/Nga atopic dermatitis mouse induced by BMAC-induced mice. Methods Clinical skin score, hematology and Serum total IgE and IgG1 of NC/Nga atopic dermatitis mice were evaluated. Moreover, the cytokine level, total cell number, Immunohistochemical staining and Histological features of axillary lymph node(ALN), draining lymph node(DLN), peripheral blood mononuclear cells(PBMCs) and dorsal skin tissue were used in NC/Nga mice. Results Orally administrated SPDJTK with concurrent administration of SPDJTK and AJ decreased the clinical skin score, total cell number of WBC, eosinophils in blood, serum total IgE & IgG1, IL-5, IL-13, IFN-$\gamma$. Also, total cell number of ALN and dorsal skin tissue, absolute cell number of CD4+, CD8+, CD3+CD69+, CD3+CCR3+, CCR3+, CD4+CXCR5+ in ALN, absolute cell number of CD3+CCR3+, CCR3+ in DLN, granulocytes in PBMCs, activation cell number of CD3+CD69+, CCR3+, total cell number of CD3+ T cell in dorsal skin tissue were significantly decreased. Furthermore, thickness of epidermis, infiltrated inflammatory immune cell and mast cell in dermis, amount of Eotaxin2 mRNA, CCR3 mRNA in dorsal skin tissue, gene expression of IL-5, IL-13 mRNA in ALN, CD4+ Th cell in dorsal skin tissue and CCR3+ eosinophils in ALN were all significantly decreased. However, total number of DLN, absolute number of CD3e+ T cell and CD19+ B cell, absolute number of CD4+, number of Th cell in DLN and gene expression of foxp3 mRNA were significantly increased significantly. Conclusions Concurrent administration of SPDJTK and AJ on atopic dermatitis in NC/Nga atopic dermatitis mouse was very effective treatment for atopic dermatitis.

• IMMUNE NETWORK
• /
• v.21 no.5
• /
• pp.34.1-34.16
• /
• 2021

Sjögren's syndrome (SS) is an autoimmune disease characterized by dryness of the mouth and eyes. The glandular dysfunction in SS involves not only T cell-mediated destruction of the glands but also autoantibodies against the type 3 muscarinic acetylcholine receptor or aquaporin 5 (AQP5) that interfere with the secretion process. Studies on the breakage of tolerance and induction of autoantibodies to these autoantigens could benefit SS patients. To break tolerance, we utilized a PmE-L peptide derived from the AQP5-homologous aquaporin of Prevotella melaninogenica (PmAqp) that contained both a B cell "E" epitope and a T cell epitope. Repeated subcutaneous immunization of C57BL/6 mice with the PmE-L peptide efficiently induced the production of Abs against the "E" epitope of mouse/human AQP5 (AQP5E), and we aimed to characterize the antigen specificity, the sequences of AQP5E-specific B cell receptors, and salivary gland phenotypes of these mice. Sera containing anti-AQP5E IgG not only stained mouse Aqp5 expressed in the submandibular glands but also detected PmApq and PmE-L by immunoblotting, suggesting molecular mimicry. Characterization of the AQP5E-specific autoantibodies selected from the screening of phage display Ab libraries and mapping of the B cell receptor repertoires revealed that the AQP5E-specific B cells acquired the ability to bind to the Ag through cumulative somatic hypermutation. Importantly, animals with anti-AQP5E Abs had decreased salivary flow rates without immune cell infiltration into the salivary glands. This model will be useful for investigating the role of anti-AQP5 autoantibodies in glandular dysfunction in SS and testing new therapeutics targeting autoantibody production.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.1
• /
• pp.265-271
• /
• 2014

Interleukin-7 (IL-7) is a potent anti-apoptotic cytokine that enhances immune effector cell functions and is essential for lymphocyte survival. While it known to induce differentiation and proliferation in some haematological malignancies, including certain types of leukaemias and lymphomas, little is known about its role in solid tumours, including breast cancer. In the current study, we investigated whether IL-7 could enhance the in vivo antitumor activity of tumor-reactive $CD8^+$ T cells with induction of IFN-${\gamma}$ in a murine breast cancer model. Human IL-7 cDNA was constructed into the eukaryotic expression plasmid pcDNA3.1, and then the recombinational pcDNA3.1-IL-7 was intratumorally injected in the TM40D BALB/C mouse graft model. Serum and intracellular IFN-${\gamma}$ levels were measured by ELISA and flow cytometry, respectively. $CD8^+$ T cell-mediated cytotoxicity was analyzed using the MTT method. Our results showed that IL-7 administration significantly inhibited tumor growth from day 15 after direct intratumoral injection of pcDNA3.1-IL-7. The anti-tumor effect correlated with a marked increase in the level of IFN-${\gamma}$ and breast cancer cells-specific CTL cytotoxicity. In vitro cytotoxicity assays showed that IL-7-treatment could augment cytolytic activity of $CD8^+$ T cells from tumor bearing mice, while anti-IFN-${\gamma}$ blocked the function of $CD8^+$ T cells, suggesting that IFN-${\gamma}$ mediated the cytolytic activity of $CD8^+$ T cells. Furthermore, in vivo neutralization of $CD8^+$ T lymphocytes by CD8 antibodies reversed the antitumor benefit of IL-7. Thus, we demonstrated that IL-7 exerts anti-tumor activity mainly through activating $CD8^+$ T cells and stimulating them to secrete IFN-${\gamma}$ in a murine breast tumor model. Based on these results, our study points to a potential novel way to treat breast cancer and may have important implications for clinical immunotherapy.

• Korean Journal of Acupuncture
• /
• v.24 no.3
• /
• pp.179-204
• /
• 2007

Objectives & Methods : The purpose of this study is to observe the effects of Angelicae Radix Pharmacopuncture(AR-P) at Joksamni(ST36) on collagen II induced arthritis in DBA/1J mice. The authors evaluated arthritis index, arthritis incidence and joint edema, and measured body weight, spleen size and stenosis rate, serum cytokine level, serum antibody level, immune cell populations In spleen, lymph node, and knee joint, and performed histological analysis of CIA mouse joint. Results : In the AR-P group, arthritis index, arthritis incidence and joint edema were decreased, and the enlargement, malformation and stenosis of spleen and the malformation of joint appeared milder than the control group. In AR-P group, the levels of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, $IFN-{\gamma}$ in serum were significantly decreased. And the level of anti-collagen II in serum was maintained lower in AR-P group than in the control group. In AR-P group, the level of $IFN-{\gamma}$ and IL-10, and $IFN-{\gamma}/IL-4$ ratio were significantly decreased, and the ratios of $CD3e^+$ cells to $CD45^+$ cells, $CD4^+$ cells to $CD8^+$ cells in spleen were similarly maintained as those of the normal group. In the AR-P group, the populations of $CD4^+/CD25^+$ cells in spleen and lymph nodes, $CD45R^+/CD69^+$ cells in lymph nodes, $CD3^+/CD69^+$ cells and $CD11b^+/Gr-1^+$ cells in knee joint were decreased. In the histological analysis, the cartilage destruction, synovial cell proliferation and the collagen fiber destruction were decreased in the AR-P group Conclusions : The results suggest that AR-P at right ST36 has a therapeutic effect on collagen-induced arthritis in mice.

• IMMUNE NETWORK
• /
• v.5 no.1
• /
• pp.23-29
• /
• 2005

Background: Interleukin-7 receptor (IL-7R) ${\alpha}$-deficient mice have small numbers of B cells and ${\alpha}{\beta}$T cells in periphery, they totally lack ${\gamma}{\delta}$T cells. In addition, the V-J recombination and transcription of TCR ${\gamma}$ genes is also severely impaired in IL-7R ${\alpha}$-deficient mice. Stat5, a signaling molecule of the IL-7R, induces germline transcription in the TCR ${\gamma}$ locus, and promotes V-J recombination and ${\gamma}{\delta}$T cell development. However, the roles for IL-7R signaling pathway in thymic or extrathymic ${\gamma}{\delta}$T cell development are largely unknown. Methods: To clarify the role of the IL-7 receptor in proliferation and survival of ${\gamma}{\delta}$T cells, we introduced the TCR ${\gamma}{\delta}$ transgene, $V_{{\gamma}2}/V{\delta}_5$, into IL-7R ${\alpha}$-deficient mice, and investigated the development of ${\gamma}{\delta}$T cells. Results: We found that $V_{{\gamma}2}/V{\delta}_5$ transgene restored ${\gamma}{\delta}$T cells in the epithelium of the small intestine (IEL) but not in the thymus and the spleen. Further addition of a bcl-2 transgene resulted in partial recovery of ${\gamma}{\delta}$T cells in the thymus and the spleen of these mice. Conclusion: Taken together, this study revealed that the IL-7R ${\alpha}$ is indispensable for proliferation and survival mainly in thymic ${\gamma}{\delta}$T cell development.

• Mycobiology
• /
• v.40 no.1
• /
• pp.47-52
• /
• 2012

$Elfvingia$ $applanata$, a medicinal mushroom belonging to Basidiomycota, has been used in the effort to cure cancers of the esophagus and stomach, and is also known to have inhibitory effects on hepatitis B virus infection. The hot water soluble fraction (as Fr. HW) was extracted from fruiting bodies of the mushroom. $In$ $vitro$ cytotoxicity tests showed that hot water extract was not cytotoxic against cancer cell lines such as Sarcoma 180, HT-29, HepG2, and TR at concentrations of 10-2,000 ${\mu}g/mL$. Intraperitoneal injection with Fr. HW resulted in a life prolongation effect of 45.2% in mice previously inoculated with Sarcoma 180. Treatment of Fr. HW resulted in a 2.53-fold increase in the numbers of murine spleen cells at a concentration of 50 ${\mu}g/mL$, compared with control. Incubation of murine spleen cells with Fr. HW at a concentration of 500 ${\mu}g/mL$ resulted in improved immune-potwntiating activity of B lymphocytes through an 8.3-folds increase in alkaline phosphatase activity, compared with control. Fr. HW generated 12.5 ${\mu}M$ of nitric oxide (NO) when cultured with RAW 264.7, a mouse macrophage cell line, at the concentration of 50 ${\mu}g/mL$, while lipopolysaccharide, a positive control, produced 15.2 ${\mu}M$ of NO. Therefore, the results suggested that antitumor activities of Fr. HW from $E.$ $applanata$ might, in part, be due to host mediated immunostimulating activity.

• IMMUNE NETWORK
• /
• v.7 no.1
• /
• pp.31-38
• /
• 2007

Background: Mizoribine (MZR) is an imidazole nucleoside isolated from Eupenicillium brefeldianum. MZR is currendy in clinical use for patients who have undergone renal transplantation. Therapeutic efficacy of MZR has also been demonstrated in rheumatoid arthritis and lupus nephritis. MZR has been shown to inhibit the proliferation or lymphocytes by interfering with inosine monophosphate dehydrogenase. Since the exact mechanism by which MZR benefits rheumatoid arthritis (RA) is not clear, we investigated the ability of MZR to direct its immunosuppressive influences on other antigen presenting cells, such as macrophages. Methods: Mouse macrophage RAW264.7 cells were stimulated with lipopolysaccharide in the presence of MZR. To elucidate the mechanism of the therapeutic efficacy in chronic inflammatory diseases, we examined the effects of MZR on the production of pro-inflammatory cytokines, nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ in macrophages. Results: MZR dose-dependendy decreased the production of nitric oxide and pro- inflammatory cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukins $1{\beta}$ (IL-${\beta}$ and IL-6 $PGE_2$. Examination of gene expression levels showed that the anti-inflammatory effect correlated with the down-regulation of inducible nitiric oxide synthase expression, cycloxygenase-2 expression and TNF-${\alpha}$ gene expression. Conclusion: In this work, we resulted whether MZR $(1.25{\sim}10{\mu}g/ml)$ inhibited macrophage activation by inhibiting secretion of pro-inflammatory cytokines, NO and $PGE_2$. These findings provide an explanation for the therapeutic efficacy of MZR in chronic inflammation-associated diseases.

• Biomolecules & Therapeutics
• /
• v.28 no.6
• /
• pp.542-548
• /
• 2020

Naturally derived diosmetin and its glycoside diosmin are known to be effective in treating inflammatory disease. This study was performed to determine whether diosmin and diosmetin have the effect of improving atopic dermatitis in a 2,4-dinitrochlorobenzen (DNCB)-induced atopic dermatitis (AD) model. DNCB was used to establish AD model in hairless mice. Skin moisture, serum immunoglobulin E (IgE), interleukin 4 (IL-4), and histological analysis were performed to measure the effectiveness of diosmin and diosmetine to improve AD. IL-4 levels were also measured in RBL-2H3 cells. Administration of diosmetin or diosmin orally inhibited the progress of DNCB-induced AD-like lesions in murine models by inhibiting transdermal water loss (TEWL) and increasing skin hydration. Diosmetin or diosmin treatment also reduced IgE and IL-4 levels in AD-induced hairless mouse serum samples. However, in the in vitro assay, only diosmetin, not diosmin, reduced the expression level of IL-4 mRNA in RBL-2H3 cells. Diosmin and diosmetine alleviated the altered epidermal thickness and immune cell infiltration in AD. Diosmin is considered effective in the cure of AD and skin inflammatory diseases by being converted into diosmetin in the body by pharmacokinetic metabolism. Thus, oral administration of diosmetin and diosmin might be a useful agent for the treatment of AD and cutaneous inflammatory diseases.