• 한국식품저장유통학회지
• /
• 제12권2호
• /
• pp.173-178
• /
• 2005

양파고추장에 대한 항암 및 면역활성을 조사한 결과는 다음과 같다. 고추장 메탄을 추출물은 aflatoxin $B_{1}$으로 돌연변이를 유도한 Salmonella typhimurium에 대하여 농도 의존적으로 항돌연변이 효과가 큰 것으로 나타났으며, 양파를 첨가하지 않은 대조구 고추장보다 양파고추장이 그 효과가 더욱 크게 나타났다. 양파고추장 메탄올추출물은 A549 및 MCF-7 암세포주에 처리한 결과 대조구에 비하여 $1,000\;{\mu}g/mL$농도에서 모두 $20\%$ 이상 그 성장을 억제하였다. 양파 고추장 메탄올추출물은 농도에 비례하여 비장세포의 증식을 유도하였고, 대조구 고추장 추출물보다 더 높은 증식을 유도하였다. 고추장 추출물을 처리한 대식세포주에서 NO의 생성이 농도 의존적으로 증가하였으며, 역시 양파고추장 추출물이 대조구 고추장 추출물보다 더 많은 NO을 생성량을 유도하였다.

• 생명과학회지
• /
• 제23권10호
• /
• pp.1199-1208
• /
• 2013

Fibroblastic reticular cells (FRC)는 림프절 T세포 지역에 구조적 골격 형성을 하며 유입 T 세포의 안내길을 제공한다. FRC는 림프절에서 T세포 생물학 발달에 기여한다. 따라서, 이것이 FRC와 T세포 사이에서 FRC의 세포생물학적 근본 기능을 알아보게 하였다. FRC 배양 상등액은 T세포 사멸을 저해하였다. FRC 상등액은 doxorubicin에 대하여 T세포에 Bcl-xL의 발현을 증가시켰다. FRC와 T세포의 공배양은 FRC의 액틴 골격의 변화와 형태적 변화를 유도하였다. 또한, FRC와 T세포의 공배양은 T 세포가 FRC 단일층에 부착하는 결과를 유도하였고 막결합형 intercellular adhesion molecule (ICAM)-1 단백질의 발현은 약간 증가한 반면 용해성 ICAM-1 (sICAM-1) 발현은 시간 의존적으로 드라마틱하게 증가하였다. FRC는 T세포에 의해 분비되는 tumor necrosis factor (TNF) 패밀리들에 의해 CCL5, CXCL1, CXCL5, CXCL16, CCL8, CXCL13와 같은 케모카인들과 ICAM-1 그리고 MMPs의 발현량을 증가시켰다. $TNF{\alpha}$가 FRC에 처리 되었을때 $NF{\kappa}B$ canonical pathway의 RelA는 핵으로 전좌 되었지만, agonistic anti-$LT{\beta}R$ antibody로 처리된 FRC에서 non-canonical $NF{\kappa}B$ pathway의 RelB의 카운터 파트너인 p100의 분해산물 p52는 핵주변부로 축적되었다. 결론적으로 FRC는 FRC와 T세포 양방향 협력을 통해 T세포 생물학적 기능을 증진한다. 이러한 상호협력 관계는 면역반응 동안 조직의 통합성과 기능을 유지하는데 도움을 줄 것으로 사료된다.

• 대한한방소아과학회지
• /
• 제24권1호
• /
• 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
• /
• 제21권5호
• /
• 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
• /
• 제15권1호
• /
• 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
• /
• 제24권3호
• /
• 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
• /
• 제5권1호
• /
• 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
• /
• 제40권1호
• /
• 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
• /
• 제7권1호
• /
• 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
• /
• 제28권6호
• /
• 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.