• IMMUNE NETWORK
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• 제5권1호
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• pp.30-35
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• 2005

Background: p38 and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) signaling are thought to have critical role in lipopolysaccharide (LPS)-induced immune response but the molecular mechanism underlying the induction of these signaling are not clear. Methods: Specific inhibitors for p38, SB203580, and for ERK, PD98059 were used. Cells were stimulated by LPS with or without specific MAPK inhibitors. Results: LPS activated inducible nitric oxide synthase (iNOS), subsequent NO productions, and pro-inflammatory cytokine gene expressions (TNF-${\alpha}$, IL-$1{\beta}$, IL-6, and IL-12). Treatment of both SB203580 and PD98059 decreased LPS-induced NO productions. Concomitant decreases in the expression of iNOS mRNA and protein were detected. SB203580 and PD98059 decreased LPS-induced gene expression of IL-$1{\beta}$ and IL-6. SB203580 increased LPS-induced expression of TNF-${\alpha}$ and IL-12, and reactive oxygen species production, but PD98059 had no effect. Conclusion: These results indicate that both p38 and ERK pathways are involved in LPS-stimulated NO synthesis, and expression of IL-$1{\beta}$ and IL-6. p38 signaling pathways are involved in LPS-induced TNF-${\alpha}$ and IL-12, and reactive oxygen species plays an important role in these signaling in macrophage.

• Journal of Yeungnam Medical Science
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• 제34권2호
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• pp.149-160
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• 2017

Streptococcus pneumoniae, pneumococcus, is the most common cause of community-acquired pneumonia (CAP). CAP is an important infectious disease with high morbidity and mortality, and it is still one of the leading causes of death worldwide. Many genetic factors of the host and various environmental factors surrounding it have been studied as important determinants of the pathophysiology and outcomes of pneumococcal infections. Various cytokines, including transforming growth factor $(TGF)-{\beta}1$, are involved in different stages of the progression of pneumococcal infection. $TGF-{\beta}1$ is a cytokine that regulates a wide range of cellular and physiological functions, including immune and inflammatory responses. This cytokine has long been known as an anti-inflammatory cytokine that is critical to preventing the progression of an acute infection to a chronic condition. On the other hand, recent studies have unveiled the diverse roles of $TGF-{\beta}1$ on different stages of pneumococcal infections other than mitigating inflammation. This review summarizes the recent findings of the role of $TGF-{\beta}1$ on the pathophysiology of pneumococcal infections, which is fundamental to developing novel therapeutic strategies for such infections in immune-compromised patients.

• 한국식품영양학회지
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• 제15권3호
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• pp.191-196
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• 2002

마늘의 주요 성분인 allicin투여 후 유도되는 사람 말초혈액의 단핵구의 유전자 발현에 미치는allicin의 효과를 규명하였다. DNA microarray를 이용하여, allicin이 chemokines, cytokine, 면역관련 유전자 및 신호전달 관련 유전자의 발현을 유도하는 것을 확인하였다. 반대로 allicin은 Th1 type의 획득면역 관련 유전자의 발현을 억제하였다. 염증세포에 있어서 allicin은 억제효과 및 자극 효과를 동시에 보여주었다. 이는 allicin이 휴지기 세포에서 먼저 증가시킨 특정 유전자의 발현을 이후에 감소시키는 결과를 보여주는 것으로 positive와 negative 효과를 발휘하는 새로운 기전을 제시하는 것이다. Allicin에 대한 광범위하고 새로운 관심을 고려해 볼 때 본 연구에서 보여주는 많은 유전자의 발현 양상은 좀 더 특정적이고 효과적인 치료법을 고안하는 데 유용할 것이다.

• Molecules and Cells
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• 제41권8호
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• pp.705-716
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• 2018

The endoplasmic reticulum (ER) is a critical organelle for protein synthesis, folding and modification, and lipid synthesis and calcium storage. Dysregulation of ER functions leads to the accumulation of misfolded- or unfolded-protein in the ER lumen, and this triggers the unfolded protein response (UPR), which restores ER homeostasis. The UPR is characterized by three distinct downstream signaling pathways that promote cell survival or apoptosis depending on the stressor, the intensity and duration of ER stress, and the cell type. Mammalian cells express the UPR transducers IRE1, PERK, and ATF6, which control transcriptional and translational responses to ER stress. Direct links between ER stress and immune responses are also evident, but the mechanisms by which UPR signaling cascades are coordinated with immunity remain unclear. This review discusses recent investigations of the roles of ER stress in immune responses that lead to differentiation, maturation, and cytokine expression in immune cells. Further understanding of how ER stress contributes to the pathogenesis of immune disorders will facilitate the development of novel therapies that target UPR pathways.

• IMMUNE NETWORK
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• 제16권1호
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• pp.44-51
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• 2016

Dendritic cells (DCs) are professional antigen presenting cells, and play an important role in the induction of antigen-specific adaptive immunity. However, some DC populations are involved in immune regulation and immune tolerance. These DC populations are believed to take part in the control of immune exaggeration and immune disorder, and maintain immune homeostasis in the body. Tolerogenic DCs (tolDCs) can be generated in vitro by genetic or pharmacological modification or by controlling the maturation stages of cytokine-derived DCs. These tolDCs have been investigated for the treatment of rheumatoid arthritis (RA) in experimental animal models. In the last decade, several in vitro and in vivo approaches have been translated into clinical trials. As of 2015, three tolDC trials for RA are on the list of ClinicalTrial.gov (www.clinicaltrials.gov). Other trials for RA are in progress and will be listed soon. In this review, we discuss the evolution of tolDC-based immunotherapy for RA and its limitations and future prospects.

• 생물정신의학
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• 제10권1호
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• pp.70-79
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• 2003

Object : Currently, the alteration of cytokine system has been known to play an important role in regard to depressive symptom. We focused on the relationship between immunological parameters and clinical improvement in major depressive disorder. Method : Data were collected on 26 patients with major depressive disorder using a 8-week prospective follow-up design. After 8-week treatment period with fluoxetine, patients were classified into a response group and a non-response group according to their psychopathological outcome as evaluated by Hamilton Depression Rating Scale. The differences of the immunological parameters between pre-treatment phase and post-treatment phase were compared among patients. The difference of those was also compared within each phase among them. The relationship between socio-demographic variables, depression, cytokine, mononuclear cells was examined by correlation analysis. Multiple regression analyses were performed to explore the predictors of clinical improvement of major depressive disorder. Result : Pre-treatment levels of IL-$1{\beta}$ in the response group were significantly higher than those in the non-response group. Pre-treatment levels of IL-$1{\beta}$ of all patients and in the response group were positively correlated with pre-treatment monocyte counts. Patients with subsequent remission showed significantly lower IL-6 values at baseline than those with non-response. Post-treatment values of IL-6 did not differ significantly among the patients. The correlation test showed more frequent relations among cytokines and mononuclear cells in the response group than in the non-responder group. Especially, serum level of IL-6 in pre-treatment phase was only significantly correlated with HAMD score after 8-week treatement phase, while other cytokines and mononuclear cells were not. Pretreatment level of IL-6 was of paramount importance in predicting clinical improvement of depressive symptom. Conclusion : The immune system of major depressive disorder patients might dichotomize the patients into subsequent responders and non-responders. Immune system might be of great influence on the clinical improvement of major depressive disorder. The mode of interaction between depression and cellular immune function and the mediators responsible for the cytokine production need to be studied further.

• 한국식품영양과학회지
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• 제46권9호
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• pp.1027-1034
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• 2017

본 연구에서는 잣피 20% 주정 추출물을 첨가한 식이로 하여 바이러스에 감염되어 면역력이 결핍된 마우스에서 면역조절 효과를 확인하고자 T, B 세포의 증식능, Th1 type cytokine과 Th2 type cytokine, NK cell activity, phagocytic activity를 확인하였다. 바이러스로 인하여 AIDS와 유사하게 면역 결핍된 마우스 모델에서 cytokine의 불균형과 T 세포와 B 세포의 proliferation이 균형적으로 회복됨을 확인하였고 바이러스로 인해 자연살해세포와 대식세포의 활성능이 감소하였지만 잣피 20% 주정 추출물의 공급 시 활성능 회복에 도움을 주는 것을 확인하였다. 따라서 잣피 20% 주정 추출물은 LP-BM5 virus로 유도한 면역 결핍 마우스 모델에서 면역조절작용에 효능이 있음을 확인하였다.

• 한국식품영양과학회지
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• 제41권4호
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• pp.494-500
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• 2012

본 연구에서는 면역억제 동물모델에서 밀리타리스 동충하초 50% 에탄올 추출물의 면역력 증강 기능을 평가하였다. 이를 위하여 C57BL/6 마우스에 cyclophosphamide를 2회 복강주사 하여 면역력을 억제한 후, 밀리타리스 동충하초 추출물을 30, 100, 300 mg/kg 용량으로 12일간 경구투여 하였다. 마우스를 희생하여 몸무게 및 면역장기 무게, 비장세포의 증식, 비장세포의 cytokine 분비능, NK 세포 활성을 측정하였다. 그 결과, cyclophosphamide 투여에 의한 면역억제는 마우스의 몸무게와 간의 무게에 영향을 주지 않았으나 흉선의 무게는 감소시켰고 비장의 무게는 증가시켰다. 밀리타리스 동충하초 추출물 투여는 마우스의 몸무게 및 면역장기 무게에 영향을 주지 않았다. Cyclophosphamide 투여는 비장세포의 증식능을 감소시켰으며 밀리타리스 동충하초 추출물은 용량 의존적으로 비장세포 증식을 증가시켜 실험에 사용한 전 용량에서 비장세포의 유의적인 증식효과를 보였다. 비장세포의 cytokine 분비능을 측정한 결과, 밀리타리스 동충하초 추출물 투여는 IL-2, IL-12, IFN-${\gamma}$, TNF-${\alpha}$ 같은 Th1 cytokine의 분비를 대조군에 비해 유의적으로 증가시켰으나, IL-4와 IL-10 같은 Th2 cytokine의 분비에는 영향을 미치지 않았다. 또한 cyclophosphamide는 NK 세포의 활성을 정상군에 비하여 유의적으로 감소시켰으며, 밀리타리스 동충하초 추출물 투여는 cyclophosphamide에 의해 저하된 NK 세포 활성을 현저하게 증가시켰다. 이상의 결과를 종합해 볼 때, 밀리타리스 동충하초는 면역력이 억제된 상황에서 면역력을 증강시키며, 이러한 면역력 증강 효과는 체액성 면역보다 세포성 면역력 증강에 기인하는 것으로 보인다.

• 한국군사과학기술학회지
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• 제16권3호
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• pp.390-397
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• 2013

Primary-cultured immune cells are widely used in research to elucidate the mechanism of inflammation including chemotaxis, production of reactive oxygen species, cytokine release and antigen presenting. Mice are one of the species of experimental animals commonly used for such studies. Immune cells can be isolated and cultured from various organs such as bone marrow, peritoneal cavity, lung, spleen. For elaborated experimental studies, immune cells should be elicited with inflammatory substances or proliferated in vitro with special media. This paper details methods of obtaining immune cells from various organs of mice and investigating immune mechanism using isolated immune cells. It contains standard protocols of isolating and culturing immune cells from bone marrow, peritoneal cavity and lymphoid organs. It also covers the methods of investigating immune mechanism such as ELISA, western blotting, confocal microscopy and ELISPOT assay. With the works in this study, we established the standardized isolation and analysis methods of primary-cultured immune cells.

• 약학회지
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• 제49권1호
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• pp.25-29
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• 2005

This study was performed to investigate the potential of pear (Pyrus pyrifolia) as a immune-modulating functional food by assay of splenocytes proliferation and induction of cytokines (IFN-${\gamma}$, IL-4) in vitro. When mouse splenocytes were exposed to various concentration (0.16, 0.31, 0.63, 1.25, 2.50 mg/ml) of pear methanol extracts (P-M) without mitogens, splenocytes proliferation (SP) was significantly increased. Also, SP to mitogens, concanavalin A (Con A) and lipopolysaccharide (LPS) were significantly increased by P-M when compared with controls. When splenocytes were cultured with P-M in the presence of Con A, cytokine (IFN-${\gamma}$, IL-4) levels in culture supernatant were significantly enhanced in a dose-dependent manner except 2.5 mg/ml when compared with control group. Therefore, our study suggest that the pear has the potential of being an immune-modulating functional food.