• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.987-991
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• 2013

Aim: To study anti-tumor effects of exosomes from class II transactivator (CIITA) gene transfected CT26 cells. Methods: In this study, we established an MHC class II molecule-expressing murine colon cancer cell line (CT26-CIITA) by transduction of the CIITA gene. Immune effects in vitro and tumor protective results in vivo were tested and monitored. Results: Exosomes from CT26-CIITA cells were found to contain a high level of MHC class II protein. When loaded on dendritic cells (DCs), exosomes from CT26-CIITA cells significantly increased expression of MHC class II molecules, CD86 and CD80, as compared to exosomes from CT26 cells. In vitro assays using co-culture of immunized splenocytes and exosome-loaded DCs demonstrated that CIITA-Exo enhanced splenocyte proliferation and IFN-${\gamma}$ production of CD4+T cells, while inhibiting IL-10 secretion. In addition, compared to exosomes from CT26 cells, CT26-CIITA-derived exosomes induced higher TNF-${\alpha}$ and IL-12 mRNA levels. A mouse tumour preventive model showed that CT26-CIITA derived exosomes significantly inhibited tumour growth in a dose-dependent manner and significantly prolonged the survival time of tumour-bearing mice. Conclusion: Our findings indicate that CT26-CIITA-released exosomes are more efficient to induce anti-tumour immune responses, suggesting a potential role of MHC class II-containing tumour exosomes as cancer vaccine candidates.

• Food Science and Biotechnology
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• 제18권6호
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• pp.1316-1321
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• 2009

Multiple beneficial properties of Opuntia ficus indica (OPF) are well established. In the present study, we have investigated the immunological role of OPF extract (OPFE) on murine splenocytes. OPFE dose- and time-dependently enhanced the proliferation of splenocytes without cytotoxicity. Our results also showed that the number of $CD4^+$ helper T cells and CD45R/$B220^+$ pan B cells increased markedly, but not $CD8^+$ cytotoxic T cells or $CD11b^+$ granulocytes/macrophages. In addition, OPFE significantly decreased the production levels of T helper (Th) 1 type cytokines, interferon (IFN)-$\gamma$, and tumor necrosis factor (TNF)-$\alpha$, although had no significantly differences in those of interleukin (IL)-4, a Th2 type cytokine in concanavalin A (Con A)-stimulated blastogenic cells. Furthermore, OPFE alone strongly increased IL-4 production and decreased TNF-$\alpha$ production even in the absence of Con A. On the basis of these results, this study suggests that OPFE enhances immunity by regulating the pro- and anti-inflammatory response, indicating that this extract exerts a marked immunomodulatory effect, confirming its usefulness as therapy for immune-related diseases.

• Journal of Microbiology and Biotechnology
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• 제23권3호
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• pp.414-421
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• 2013

Lactic acid bacteria (LAB) in fermented foods have attracted considerable attention recently as treatment options for immune diseases, the incidence of which has been increasing worldwide. The ability of 500 strains of LAB, isolated from kimchi, to induce TNF-${\alpha}$ production in peritoneal macrophages was investigated. Lactobacillus plantarum HY7712 most strongly induced TNF-${\alpha}$ production as well as NF-${\kappa}B$ activation. However, HY7712 inhibited NF-${\kappa}B$ activation in LPS-stimulated peritoneal macrophages. When HY7712 was orally treated in cyclophosphamide (CP)-immunosuppressed mice for 5 or 15 days, it reversed the body and spleen weights, blood RBC and WBC levels, and splenocyte and bone marrow cells that were reduced by CP. Orally administered HY7712 increased concanavalin A-induced T cell proliferation to 84.5% of the normal group on day 15, although treatment with CP alone markedly reduced it to 53.7% of the normal group. Furthermore, orally administered HY7712 significantly induced the expressions of IL-2 and IFN-${\gamma}$ in ConA-induced splenic cytotoxic T cells of CP-treated mice. Orally administered HY7712 restored the CP-impaired phagocytosis of macrophages in mice. Orally administered HY7712 also restored the cytotoxicity of NK and cytotoxic T cells derived from spleen and bone marrow against YAC-1 in CP-immunosuppressed mice. Based on these findings, orally administered HY7712 may accelerate the recovery of cyclophosphamide-caused immunosuppression, without evident side effects, by immunopotentiating NK and Tc cells, and may provide a mechanistic basis for using HY7712 as an alternative means in lessening chemotherapyinduced immunosuppression in cancer patients.

• Journal of Microbiology and Biotechnology
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• 제29권5호
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• pp.704-712
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• 2019

Although nanometric dead Lactobacillus plantarum has emerged as a potentially important modulator of immune responses, its underlying mechanism of action has not been fully understood. This study aimed to identify the detailed biochemical mechanism of immune modulation by micronized and heat-treated L. plantarum LM1004 (MHT-LM1004, <$1{\mu}m$ in size). MHT-LM1004 was prepared from L. plantarum LM1004 via culture in a specifically designed membrane bioreactor and heat treatment. MHT-LM1004 was shown to effectively induce the secretion of $TNF-{\alpha}$ and IL-6 and the mRNA expression of inducible nitric oxide synthase (iNOS). MHT-LM1004 enhanced the expression of TLR-2, phosphorylation of MAPKs (ERK), and nuclear translocation of $NF-{\kappa}B$ in a dose-dependent manner. Oral administration of MHT-LM1004 ($4{\times}10^9$ or $4{\times}10^{11}cells/kg$ mouse body weight) increased the splenocyte proliferation and serum cytokine levels. These results suggested that MHT-LM1004 effectively enhances early innate immunity by activating macrophages via the TLR-2/MAPK/$NF-{\kappa}B$ signalling pathway and that this pathway is one of the major routes in immune modulation by the Lactobacillus species.

• IMMUNE NETWORK
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• 제16권2호
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• pp.140-145
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• 2016

Ophiocordyceps sinensis is a natural fungus that has been valued as a health food and used in traditional Chinese medicine for centuries. The fungus is parasitic and colonizes insect larva. Naturally occurring O. sinensis thrives at high altitude in cold and grassy alpine meadows on the Himalayan mountain ranges. Wild Ophiocordyceps is becoming increasingly rare in its natural habitat, and its price limits its use in clinical practice. Therefore, the development of a standardized alternative is a great focus of research to allow the use of Ophiocordyceps as a medicine. To develop an alternative for wild Ophiocordyceps, a refined standardized extract, CBG-CS-2, was produced by artificial fermentation and extraction of the mycelial strain Paecilomyces hepiali CBG-CS-1, which originated from wild O. sinensis. In this study, we analyzed the in vitro immune-modulating effect of CBG-CS-2 on natural killer cells and B and T lymphocytes. CBG-CS-2 stimulated splenocyte proliferation and enhanced Th1-type cytokine expression in the mouse splenocytes. Importantly, in vitro CBG-CS-2 treatment enhanced the killing activity of the NK-92MI natural killer cell line. These results indicate that the mycelial culture extract prepared from Ophiocordyceps exhibits immune-modulating activity, as was observed in vivo and this suggests its possible use in the treatment of diseases caused by abnormal immune function.

• IMMUNE NETWORK
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• 제10권2호
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• pp.64-74
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• 2010

Background: The present study was undertaken to examine the immunological effects of pentabrominated diphenyl ether (penta-BDE) and decabrominated diphenyl ether (deca-BDE) on the immune system of the dams and the developmental immune system of the offsprings. Methods: In this study, mated female C57BL/6J mice were orally administered penta-BDE, deca-BDE or corn oil for 5 weeks, from gestational day 6 to lactational day 21. Results: The body weight of PND21 exposed to penta-BDE was significantly decreased relative to control mice, but that of post-natal day 63 (PND63) were recovered. Orally dosed dams with penta-BDE had significantly smaller absolute and relative spleen masses than control mice. Absolute and relative spleen and thymus masses of PND21 exposed to penta-BDE were significantly decreased over control. The exposure of dams and PND21 with penta-BDE reduced the number of splenocytes and thymocytes. As results of hematologic analysis, percentage WBC and percentage neutrophils increased in dams with deca-BDE. Splenic T cell proliferation in dams and PND21 exposed to penta-BDE was increased, and there were no significant difference in splenic B cell proliferation in all treatment groups. As results of flow cytometric analysis of splenocyte, percentage total T cell, Th cell and Tc cell in PND21 exposed to penta-BDE was slightly increased, and percentage macrophage in dams and PND21 exposed to deca-BDE was decreased. The ELISA results of antibody production show no significant difference in all treatment groups relative to controls. Conclusion: These results imply that PBDEs given to the dam were transferred to the offspring during gestation and lactation, and PBDEs transferred from the dam affect immune system of offspring.

• 한국약용작물학회지
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• 제24권5호
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• pp.408-419
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• 2016

Background: In recent years, adjuvants have received increasing attention owing to the development of purified subunit and synthetic vaccines which are poor immunogens and require additional adjuvants to evoke an immune response. Therefore, immunologic adjuvants have been developed and tested. Plant polysaccharides have been recognized as effective biological response modifiers with low toxicity. Methods and Results: In this study, the polysaccharide from the aboveground part of Astragalus membranaceus Bunge containing immunomodulating arabino-3,6-galactan was evaluated for its hemolytic activity and adjuvant potential in the specific cellular and humoral immune responses to ovalbumin. The polysaccharide from the aboveground part of Astragalus membranaceus Bunge was co-immunized with the purified Vi capsular polysaccharide of Salmonella typhi vaccine in mice. The polysaccharide from the aboveground part of Astragalus membranaceus Bunge did not induce any hemolytic activity or side effects at doses up to $500{\mu}g/m{\ell}$. The concanavalin A-, lipopolysaccharide-, and ovalbumin-induced splenocyte proliferation and serum ovalbumin-specific IgG, IgG1 and IgG2b antibody titers in immunized mice were significantly enhanced by AMA. Pharmacological data revealed that the polysaccharide from the aboveground part of Astragalus membranaceus Bunge increased antigen-specific antibody levels in immunized mice. The polysaccharide from the aboveground part of Astragalus membranaceus Bunge-adjuvanted purified Vi capsular polysaccharide of Salmonella typhi vaccine improved the proliferation of splenocytes and macrophages as well as stimulated cytokine production. Conclusions: These results suggest that the polysaccharide from the aboveground part of Astragalus membranaceus Bunge-adjuvanted vaccines enhanced humoral and cellular immunity and that the polysaccharide from the aboveground part of Astragalus membranaceus Bunge is a safe and efficacious adjuvant candidate suitable for use in prophylactic and therapeutic vaccines.

• 한국식품영양과학회지
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• 제44권11호
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• pp.1621-1628
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• 2015

본 연구는 참모자반 조다당 추출물(SFP) 및 에탄올 추출물(SFE)의 면역 활성에 관하여 비교하기 위하여 선천면역계에서 중요한 역할을 수행하는 대표적인 세포인 대식세포와 후천면역계에서 중추적인 역할을 수행하는 비장세포에 각각 SFP와 SFE를 처리하여 각각의 면역세포의 세포 증식률과 사이토카인 분비능에 미치는 영향에 관하여 측정하여 보았다. 대식세포에 SFP 및 SFE를 각각 농도별(12.5, 25, 50, $100{\mu}g/mL$)로 처리하였을 때 두 추출물 모두 대식세포에 대한 세포독성을 유발하지 않았으며, 대식세포의 활성과 밀접한 관련을 가지는 NO, iNOS 및 cytokine의 분비능에 미치는 영향에 관하여 알아본 결과 SFP 처리구에서도 농도 의존적으로 분비능이 증가되는 것으로 관찰되었다. 또한 마우스 비장에서 유리된 비장세포에 SFP 및 SFE를 처리하였을 때 SFP의 처리구에서 비장세포의 증식능 및 면역 활성과 밀접한 관련을 갖는 Th1 type의 cytokine인 IL-2 및 $IFN-{\gamma}$의 분비능이 유의적으로 증가되는 반면, 알레르기를 유도하는 것으로 알려진 Th2 type의 cytokine인 IL-4의 함량에는 영향을 미치지 않는 것으로 관찰되었다. 따라서 참모자반 당류 추출물은 선천면역계와 후천면역계를 담당하는 면역세포인 대식세포 및 비장세포의 활성에 중요한 영향을 미치는 것으로 사료된다.

• 한국미생물·생명공학회지
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• 제31권4호
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• pp.355-361
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• 2003

사람 분변으로부터 대식세포 활성 증강효능이 있는 유산균을 선별하여 이를 동정한 결과 P. pentosaceus 동정되었으며, 이 균주를 P. pentosaceus EROM101로 명명하였다. P. pentosaceus EROM101의 면역증강 및 항암활성을 알아보기 위하여 실험동물에게 3주간 생균 및 파쇄액을 경구 투여한 뒤 대식세포와 비장세포의 활성화를 측정하였으며, 동시에 소장점막상피세포에서 생산되는 IgA의 함량을 측정하였다. P. pentosaceus EROM101의 경구 투여는 대식세포 및 비장세포의 분열을 촉진하여 면역증강 기능이 있는 것으로 나타났다. 특히, 생균보다 파쇄액에서 활성이 더 뛰어난 것으로 나타나, P. pentosaceus EROM101은 장내에서 생균으로 서식하여 지속적으로 면역증강 기능을 나타내는 것이 아닌 세포 구성물에서 면역증강활성이 있는 것으로 사료되었다. 또한, 소장점막상피세포에서 IgA의 분비량에서도 대조군보다 약 4배이상의 IgA 생산량을 증가시켜 장관면역 활성화 기능이 있는 것으로 판단되었다. 또한 P. pentosaceus EROM101 파쇄액이 Sarcoma 180 복수암세포를 이식해 준 실험동물 내에서 복수암성장을 억제하였으나, Sarcoma 180 세포열에 대한 세포독성을 나타내지 않아 면역증강에 의해서 항암 활성이 나타난 것으로 추측되었다. 이상의 연구결과에서 P. pentosaceus EROM101은 면역증강 능력이 있으며, 동시에 항암 활성을 기대할 수 있을 것으로 사료된다.

• 한국식품영양과학회지
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• 제45권3호
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• pp.445-451
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• 2016

본 연구는 고사리 및 취나물과 같은 산채가 첨가된 된장 및 일반 된장의 면역 활성을 비교하기 위하여 선천면역계의 대표적인 세포인 대식세포와 적응면역계에서 중추적인 역할을 수행하는 비장세포에 각각 산채첨가 된장 추출물(WPDJ) 및 일반 된장(DJ) 추출물을 처리하여 각각의 면역세포의 세포증식률과 사이토카인 분비능에 미치는 영향에 관하여 측정하여 보았다. 대식세포 및 비장세포에 WPDJ 및 DJ를 125, 250 및 $500{\mu}g/mL$의 농도로 처리하였을 때 두 추출물 모두 대식세포 및 비장세포에 대한 세포독성을 유발하지 않았으며, 농도 의존적으로 세포증식률을 증가시키는 것으로 관찰되었다. 대식세포의 사이토카인의 분비능에 관하여 알아본 결과 WPDJ 처리구에서 더 높게 증가하는 것으로 관찰되었다. 또한 마우스 비장에서 유리된 비장세포에 WPDJ 및 DJ를 125, 250 및 $500{\mu}g/mL$의 농도로 처리하였을 때 Th1 type의 사이토카인인 IL-2와 IFN-${\gamma}$의 분비능은 유의적으로 증가한 반면, 알레르기를 유도하는 것으로 알려진 Th2 type의 사이토카인인 IL-4의 생성에는 영향을 미치지 않는 것으로 관찰되었다. 따라서 산채를 첨가하여 제조한 된장은 일반 된장보다 면역 활성을 더 높게 증가시키는 것으로 생각한다.