• Journal of Microbiology and Biotechnology
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• 제24권1호
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• pp.127-131
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• 2014

While searching for lactic acid bacteria that can restore aging-impaired immune responses, we isolated the Toll-like receptor (TLR) 2/NF-${\kappa}B$-activating strain Lactobacillus plantarum HY7712 from kimchi and investigated its immunomodulating effect in whole-body ${\gamma}$-irradiated mice. Exposure to HY7712 strongly activated NF-${\kappa}B$ signaling in RAW264.7 cells, but inhibited lipopolysaccharide-stimulated NF-${\kappa}B$ activation. Moreover, HY7712 protected against the downregulation of interferon (IFN)-${\gamma}$ and upregulation of interleukin (IL)-13 caused by ${\gamma}$-irradiation in mice. In mice, ${\gamma}$-irradiation impaired NK-cell activity against YAC-1 tumor cells, but following HY7712 exposure, the activity of NK cells was restored to 91.5% of the level measured in control mice (p < 0.05). These findings suggest that HY7712 activates the TLR2/NF-${\kappa}B$ signaling pathway and protects against the impairment of NK-cell activity caused by ${\gamma}$-irradiation or aging.

• Journal of Microbiology and Biotechnology
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• 제27권6호
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• pp.1189-1197
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• 2017

Lichen-forming fungi are known to have various biological activities, such as antioxidant, antimicrobial, antitumor, antiviral, anti-inflammation, and anti proliferative effects. However, the immunosuppressive effects of Bryoria sp. extract (BSE) have not previously been investigated. In this study, the inhibitory activity of BSE on the proliferation of $CD8^+$ T cells and the mixed lymphocytes reaction (MLR) was evaluated in vitro. BSE was non-toxic in spleen cells and suppressed the growth of splenocytes induced by anti-CD3. The suppressed cell population in spleen cells consisted of $CD8^+$ T cells and their proliferation was inhibited by the treatment with BSE. This extract significantly suppressed the IL-2 associated with T cell growth and $IFN-{\gamma}$ as the $CD8^+$ T cell marker. Furthermore, BSE reduced the expression of the IL-2 receptor alpha chain ($IL-2R{\alpha}$) on $CD8^+$ T cells and CD86 on dendritic cells by acting as antigen-presenting cells. Finally, the MLR produced by the co-culture of C57BL/6 and MMC-treated BALB/c was suppressed by BSE. IL-2, $IFN-{\gamma}$, and CD69 on $CD8^+$ T cells in MLR condition were inhibited by BSE. These results indicate that BSE inhibits the MLR via the suppression of $IL-2R{\alpha}$ expression in $CD8^+$ T cells. BSE has the potential to be developed as an anti-immunosuppression agent for organ transplants.

• Molecules and Cells
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• 제24권1호
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• pp.132-138
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• 2007

4-1BB (CD137), a member of the tumor necrosis factor receptor superfamily, is expressed on activated T-cells, and 4-1BB signaling due to interaction with 4-1BB ligand or ligation with anti-4-1BB monoclonal antibody (mAb) costimulates T cells. It has been shown that administration of anti-4-1BB mAb induces anti-tumor immunity in mice, but the nature of the cellular subsets responsible for this immunity is uncertain. In this study we found that anti-4-1BB mAb administration to B16F10 melanoma-bearing mice induced marked expansion of $CD11c^+CD8^+$ T-cells in parallel with suppression of pulmonary tumors. The mAb-treated mice produced higher levels of $IFN-{\gamma}$ in their tumor tissues, spleen and lymph nodes than mice exposed to control antibody. When the $CD11c^+CD8^+$ T-cells were purified and re-stimulated in vitro, they produced high levels of the Th1 cytokines, $IFN-{\gamma}$ and IL-2, but low levels of the Th2 cytokines, IL-4 and IL-10. Furthermore, they expressed high levels of 4-1BB and CD107a, a marker of activated cytotoxic T-lymphocytes. Our results suggest that $CD11c^+CD8^+$ T-cells play a role in the anti-tumor immunity induced by anti-4-1BB mAb.

• 동의생리병리학회지
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• 제22권2호
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• pp.410-414
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• 2008

In the recently, increased concern has been focused on the pharmacology and clinical utility of herbal extracts and derivatives as a drug or adjunct to chemotherapy and immunotherapy. Here we investigated the modulatory effects of the extract of Zanthoxyli Pericarpium (ZP) in production of inflammatory mediators from Raw264.7 cells and expression of CD86, CD14, toll-like receptor (TLR)-4 from peritoneal macrophage. ZP enhanced the production of NO and $TNF-{\alpha}$ as well as mRNA expression of iNOS and $TNF-{\alpha}$. Treatment of peritoneal macrophage with ZP resulted in the enhanced cell-surface molecules expression of CD86, CD14 and TLR4. We assayed the effect of ZP in cell proliferation and production of $IFN-{\gamma},\;TNF-{\alpha}$. ZP increased Con A-induced cell proliferation and production of $IFN-{\gamma},\;TNF-{\alpha}$. These studies indicate that ZP induces macrophage activation and suggest the possible use of ZP in macrophage-based immunotherapies

• Parasites, Hosts and Diseases
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• 제57권1호
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• pp.33-38
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• 2019

Trichomoniasis is a common sexually transmitted infection caused by Trichomonas vaginalis, which actually does not exist a vaccine for control or prevention. Thus, the identification of new and potent immunogens in T. vaginalis, which can contribute to the development of a vaccine against this parasite, is necessary. Therefore, the aim of this work was to evaluate the potential of a recombinant Transient Receptor Potential-like channel of T. vaginalis (TvTRPV), as a promising immunogen in BALB/c mice. First, TvTRPV was cloned and expressed as a recombinant protein in Escherichia coli BL21 cells and purified by nickel affinity. Next, BALB/c mice were immunized and the antibody levels in mice serum and cytokines from the supernatant of macrophages and from co-culture systems were evaluated. Recombinant TvTRPV triggered high levels of specific total IgG in sera from the immunized mice. Also, a statistically significant increase of cytokines: $IL-1{\beta}$, IL-6, and $TNF-{\alpha}$ after stimulation with the corresponding antigens in vitro, was identified. Moreover, co-cultures using $CD4^+$ T cells from immunized mice were able to identify higher levels of IL-10 and $IFN-{\gamma}$. These results were useful to validate the immunogenicity of TvTRPV in BALB/c mice, where IL-10-$IFN-{\gamma}$-secreting cells could play a role in infection control, supporting the potential of TvTRPV as a promising target for vaccine against T. vaginalis.

• BMB Reports
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• 제47권3호
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• pp.122-129
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• 2014

Although considerable progress has been made in understanding how tumors evade immune surveillance, measures to counter the same have not kept pace with the advances made in designing effective strategies. 4-1BB (CD137; TNFRS9), an activation-induced costimulatory molecule, is an important regulator of immune responses. Targeting 4-1BB or its natural ligand 4-1BB ligand (4-1BBL) has important implications in many clinical conditions, including cancer. In-depth analysis revealed that 4-1BB-mediated anti-cancer effects are based on its ability to induce activation of cytotoxic T lymphocytes (CTL), and among others, high amounts of IFN-${\gamma}$. In this review, we will discuss the various aspects of 4-1BB-mediated anti-tumor responses, the basis of such responses, and future directions.

• BMB Reports
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• 제52권5호
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• pp.336-341
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• 2019

The cGAS-STING pathway plays an important role in pathogen-induced activation of the innate immune response. The 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) found predominantly in the synovial fluid of osteoarthritis (OA) patients increases the expression of catabolic factors via the toll-like receptor-2 (TLR-2) signaling pathway. In this study, we investigated whether 29-kDa FN-f induces inflammatory responses via the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon gene (STING) pathway in human primary chondrocytes. The levels of cGAS and STING were elevated in OA cartilage compared with normal cartilage. Long-term treatment of chondrocytes with 29-kDa FN-f activated the cGAS/STING pathway together with the increased level of gamma-H2AX, a marker of DNA breaks. In addition, the expression of pro-inflammatory cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF/CSF-2), granulocyte colony-stimulating factor (G-CSF/CSF-3), and type I interferon ($IFN-{\alpha}$), was increased more than 100-fold in 29-kDa FN-f-treated chondrocytes. However, knockdown of cGAS and STING suppressed 29-kDa FN-f-induced expression of GM-CSF, G-CSF, and $IFN-{\alpha}$ together with the decreased activation of TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), and inhibitor protein ${\kappa}B{\alpha}$ ($I{\kappa}B{\alpha}$). Furthermore, NOD2 or TLR-2 knockdown suppressed the expression of GM-CSF, G-CSF, and $IFN-{\alpha}$ as well as decreased the activation of the cGAS/STING pathway in 29-kDa FN-f-treated chondrocytes. These data demonstrate that the cGAS/STING/TBK1/IRF3 pathway plays a critical role in 29-kDa FN-f-induced expression of pro-inflammatory cytokines.

• Clinical and Experimental Pediatrics
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• 제49권4호
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• pp.439-445
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• 2006

목 적 : ${\alpha}$-Galactosylceramide (GalCer)로 자극한 자연살상 T 세포(NKT)는 CD1d 및 T 세포 수용체(T cell receptor) 의존적으로 일부 백혈병에서 항암효과를 발현하나, CD1d음성인 신경모세포종에서는 세포독성을 유도할 수 없다. 이들 NKT세포의 활성화 시 분비되는 많은 양의 사이토카인의 직접적인 항암효과에 대해서는 소수의 보고가 있다. 본 연구에서는 hCD1d/${\alpha}$-GalCer tetramer로 NKT세포를 자극하여 얻은 상청액(supernatant)을 이용하여 NKT세포에 의한 신경모세포종의 치료적 접근의 가능성을 알아보았다. 방 법 : 신경모세포종 세포 주를 IMDM 배지에 배양하였고, NKT세포에서 분비되는 사이토카인 양은 cytometric bead array (CBA)분석으로 측정하였다. 세포 생존율은 calcein-AM 형광물질을 이용하여 digital image microscopy scanning (DIMSCAN)으로 측정하였고 특이 세포고사(specific apoptosis)는 annexin V and 7-AAD 염색 후 유식세포분석기를 통하여 산출하였다. 결 과 : 활성화된 NKT세포는 많은 양의 IL-2, IL-4, INF-${\gamma}$와 TNF-${\alpha}$을 분비하였다. NKT 자극 후 얻어진 상청액은 8개의 신경모세포종 세포 주 중 4개에서 의미있는 세포독성을 나타냈으며, 그 기전은 annexin-V 염색이나 pancaspase 억제제의 전 처치 실험으로 세포고사을 통하여 유도됨을 알 수 있었다. 그리고 이들 세포고사 유도는 anti-TNF-${\alpha}$, anti-IFN-${\gamma}$ 중화항체의 단독투여 시 현저히 감소하였고 동시투여 시에는 완전하게 억제되었다. 결 론 : NKT 세포의 활성화에 의해 분비된 IFN-${\gamma}$와 TNF${\alpha}$가 일부 신경모세포종 세포 주에서 협동적 세포 독성을 유도하였다.

• IMMUNE NETWORK
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• 제3권3호
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• pp.188-200
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• 2003

Background: Immunization of dendritic cells (DCs) pulsed with tumor antigen can activate tumor-specific cytotoxic T lymphocytes (CTL) that are responsible for protection and regression. In this study, we examined whether the uptake of necrotic tumor cells could modulate DC phenotypes and whether the immunization of necrotic tumor cell-loaded DCs could elicit efficient tumor specific immune responses followed by a regression of established tumor burdens. Methods: We prepared necrotic tumor cell-pulsed DCs for the therapeutic vaccination and investigated their phenotypic characteristics, the immune responses induced by these DCs, and therapeutic vaccine efficacy against colon carcinoma in vivo. Several parameters including phagocytosis of tumor cells, surface antigen expression, chemokine receptor expression, IL-12 production, and NK as well as CTL activation were assessed to characterize the immune response. Results: DCs derived from mouse bone marrow efficiently phagocytosed necrotic tumor cells and after the uptake, they produced remarkably increased levels of IL-12. A decreased CCR1 and increased CCR7 expression on DCs was also observed after the tumor uptake, suggesting that antigen uptake could induce DC maturation. Furthermore, co-culturing of DCs with NK cells in vitro enhanced IL-12 production in DCs and IFN-${\gamma}$ production in NK cells, which was significantly dependent on IL-12 production and cell-to-cell contact. Immunization of necrotic tumor cell-loaded DCs induced cytotoxic T lymphocytes as well as NK activation, and protected mice against subsequent tumor challenge. In addition, intratumoral or contra-lateral immunization of these DCs not only inhibited the growth of established tumors, but also eradicated tumors in more than 60% of tumor-bearing mice. Conclusion: Our data indicate that production of IL-12, chemokine receptor expression and NK as well as CTL activation may serve as major parameters in assessing the effect of tumor cell-pulsed DC vaccine. Therefore, DCs loaded with necrotic tumor cells offer a rational strategy to treat tumors and eventually lead to prolonged survival.

• 생명과학회지
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• 제21권1호
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• pp.22-30
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• 2011

아포지방단백 A-I (apoA-I)은 항염증 및 항산화 작용을 가지고 있는 것으로 알려져 있다. 본 논문에서는 인간 혈액의 호중구를 이용하여 in vitro 상태에서 세포사멸과 시토카인의 분비 과정에 미치는 apoA-I의 영향을 조사하였다. 인간 호중구에 apoA-I을 처리한 결과 세포사멸의 정도가 감소되었다. 또한, apoA-I을 함유하는 고밀도 지방단백(HDL)에 의하여도 세포사멸은 현저히 감소되었다. HDL이 결합하는 수용체인 scavenger 수용체 B-1에 대한 항체에 의하여도 세포사멸은 억제되었다. ApoA-I을 20 시간 처리한 세포의 배양액내 인터루킨-8, 인터페론-유도단백질 10(IP-10) 및 종양괴사인자-α의 분비가 현저히 증가하였다. 호중구에 인터페론 감마와 apoA-I을 동시 처리하였을 때 시토카인 중에서 IP-10과 종양괴사인자-$\alpha$의 분비가 단독으로 처리한 경우에 비해 현저히 증가되었다. 이러한 결과들은 인간 혈액 호중구에 apoA-I을 처리한 경우 호중구가 활성화되고 호중구의 세포사멸이 지연된다는 것을 제시하는 것으로 apoA-I이 호중구에 대하여 염증성 인자로 작용할 것으로 추정된다.