• IMMUNE NETWORK
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• 제9권3호
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• pp.84-89
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• 2009

The main stream of CD137 studies has been directed to the function of CD137 in $CD8^+$ T-cell immunity, including its anti-tumor activity, and paradoxically the immunosuppressive activity of CD137, which proves to be of a great therapeutic potential for animal models of a variety of autoimmune and inflammatory diseases. Recent studies, however, add complexes to the biology of CD137. Accumulating is evidence supporting that there exists a bidirectional signal transduction pathway for the CD137 receptor and its ligand (CD137L). CD137/CD137L interactions are involved in the network of hematopoietic and nonhematopoietic cells in addition to the well characterized antigen-presenting cell-T cell interactions. Signaling through CD137L plays a critical role in the differentiation of myeloid cells and their cellular activities, suggesting that CD137L signals trigger and sustain inflammation. The overall consequence might be that the amplified inflammation by CD137L enhances the T-cell activity together with CD137 signals by upregulating costimulatory molecules, MHC molecules, cell adhesion molecules, cytokines, and chemokines. Solving this outstanding issue is urgent and will have an important clinical implication.

• IMMUNE NETWORK
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• 제12권5호
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• pp.176-180
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• 2012

Although the majority of research on CD137 has been directed to T cells, it is becoming clear that this molecule has distinct functions in other lineages of cells, including non-hematopoietic cells. In particular, emerging evidence suggests that the CD137-its ligand (CD137L) network involving immune cells and non-immune cells, directly or indirectly regulates inflammation in both positive and negative manners. Bidirectional signaling through both CD137 and CD137L is critical in the evolution of inflammation: 1) CD137L signaling plays an indispensible role in the activation and recruitment of neutrophils by inducing the production of proinflammatory cytokines and chemokines in hematopoietic and non-hematopoietic cells such as macrophages, endothelial cells and epithelial cells; 2) CD137 signaling in NK cells and T cells is required for their activation and can influence other cells participating in inflammation via either their production of proinflammatory cytokines or engagement of CD137L by their cell surface CD137: 3) CD137 signaling can suppress inflammation by controlling regulatory activities of dendritic cells and regulatory T cells. As recognition grows of the role of dysregulated CD137 or CD137L stimulation in inflammatory diseases, significant efforts will be needed to develop antagonists to CD137 or CD137L.

• 대한소아치과학회지
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• 제35권4호
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• pp.597-606
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• 2008

본 연구는 TNFR family인 CD137 및 RANK, 파골세포의 CD137L와 T 세포의 RANKL 간의 역신호에 의한 이들 세포 의 역할을 알아보고자 하였다. 이에 RANKL 및 CD137L 자극으로 유도되는 역신호 전달에 의한 T 세포 활성과 파골세포분 화에 미치는 영향을 규명하고자 웅성 생쥐의 골수세포와 T 세포를 공동배양하여 다음과 같은 결과를 얻었다. 1. 생쥐 단핵세포주 및 골수유도 단핵전구세포에서 CD137L이 발현되며, CD137L 단클론 항체로 자극을 주었을 경우 파 골세포 표지단백질인 TRAP 양성 파골세포의 형성이 억제되었다. 2. 활성화된 $CD4^+$ 및 $CD8^+$ T 세포에서 RANKL을 발현하였으며 RANKL의 유사 수용체인 OPG 재조합 단백질을 처리 하여 $CD4^+$ 및 $CD8^+$ T 세포의 세포증식이 억제되었다. 이 연구의 결과는 CD137 자극에 의한 T 세포활성 및 RANK 자극에 의한 파골세포분화 및 활성이 각각 수용체에 결합하 는 라이겐드의 역신호에 의해 억제되었는데, 이는 파골세포와 T 세포의 과도한 활성을 제어하는 생체의 항상성조절에 관여하 는 기전으로 생각된다.

• IMMUNE NETWORK
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• 제15권3호
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• pp.121-124
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• 2015

Now, it has been being accepted that reverse signaling through CD137 ligand (CD137L) plays an important role in vivo during hematopoiesis and in immune regulation. However, due to technical difficulty in dissecting both directional signaling events simultaneously in vivo, most biological activities caused by CD137-CD137L interactions are considered as results from signaling events of the CD137 receptor. To make the story more complex, $CD137^{-/-}$ and $CD137L^{-/-}$ mice have increased or decreased immune responses in a context-dependent manner. In this Mini review, I will try to provide a plausible explanation for how CD137L signaling is controlled during immune responses.

• IMMUNE NETWORK
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• 제11권4호
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• pp.216-222
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• 2011

Background: The ligand for CD137 (CD137L; also called 4-1BBL) is mainly expressed on activated APCs such as dendritic cells, B cells and macrophages. Even though CD137L functions as a trigger of the CD137 signaling pathway for T cell activation and expansion, engagement of CD137L can deliver a signal leading to the production of proinflammatory cytokines in macrophages. Methods: We generated cell-permeable TAT-CD137L cytoplasmic domain fusion protein (TAT-CD137Lct) and examined its ability to initiate the CD137L reverse signaling pathway. Results: Treatment of TAT-CD137Lct induced the production of high levels of IL-6 and TNF-${\alpha}$ mRNAs and proteins in peritoneal macrophages. TAT-CD137Lct increased phosphorylation of Erk, p38 MAPK and Jnk, and activated transcription factors C/EBP and CREB. However, TAT-CD137Lct did not visibly affect the degradation of the inhibitor of NF-${\kappa}B$ ($IkB{\alpha}$). We further demonstrated that JNK activation was required for TAT-CD137Lct-induced production of TNF-${\alpha}$, while activation of Erk and p38 MAPK were involved in IL-6 and TNF-${\alpha}$ production. Conclusion: Our results suggest that TATCD137Lct is an effective activator for the CD137L reverse signaling pathway.

• 대한이식학회지
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• 제28권3호
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• pp.113-120
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• 2014

Two-signal models are useful in explaining various types of immune responses. In particular, secondary, so-called costimulatory, signals are critically required for the process of T-cell activation, survival, differentiation, and memory formation. Early studies in rodent models showed that targeting T-cell costimulatory pathways elicits immunological tolerance, providing a basis for development of costimulatory therapeutics in allograft rejection. However, as the classic definition of T-cell costimulation continues to evolve, simple blockade of costimulatory pathways has limitations in prevention of allograft rejection. Furthermore, functions of costimulatory molecules are much more diverse than initially anticipated and beyond T cells. In this mini-review, we will discuss CD137-CD137L bidirectional signals as examples showing that two-signals can be applicable to multiple phases of immune responses.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2006년도 춘계학술대회
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• pp.40-51
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• 2006

To investigate the association between Korean red ginseng (KRG) intake in HIV-1 infected patients and occurrence of grossly deleted nef genes ($g{\Delta}nef$), we characterized nef genes in 10 long-term slow progressors (LTSP) infected with HIV-1 subtype B and 34 control patients. LTSP was defined whose the annual decrease in CD4 T cells was less than $20/{\mu}l$ over 10 years in the absence of antiretroviral therapy. They were treated with KRG for a prolonged period. Nef genes were amplified from peripheral blood mononuclear cells (PBMC) using nested PCR and products were sequenced directly. Patient CD4 T cell counts decreased from $444{\pm}207/{\mu}l$ to $294{\pm}177/{\mu}l$ over $136{\pm}23$ months of KRG intake. This corresponds to an annual decrease in the level of CD4 T cells of $13.3/{\mu}l$. A total of 479 nef genes were amplified from 137 PBMC samples. Nine out of the 10 patients, 47 (34.3%) out of the 137 samples, and 92 out of the 479 genes revealed $g{\Delta}nef$. The deletion extended outside the nef gene in 25 $g{\Delta}nef$ obtained from 6 patients. The proportion of samples with $g{\Delta}nef$ (34.3%) was significantly higher than 4.8% in control patients (P<0.001). In addition, it significantly increased as the duration of KRG intake prolongs (P<0.01). These data suggest the possibility that occurrence of $g{\Delta}nef$ might be associated with long-term intake of KRG.

• IMMUNE NETWORK
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• 제8권4호
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• pp.137-142
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• 2008

Background: CD11c, also known as integrin alpha x, is one of the optimum markers of dendritic cells. However, the regulation of the CD11c expression in mouse has not been identified yet. In this study, in order to analyze the regulation of CD11c expression, the promoter of CD11c was cloned and characterized. Methods: To identify the promoter portion, various sizes of what are considered to be CD11c promoter fragments was amplified by polymerase chain reaction (PCR), using mouse genomic DNA as a template. After sequence was obtained, these fragments were transfected into various cell lines including mouse dendritic cell lines such as JAWSII and DC2.4 and L929 as control cell line.. The promoter activity of three promoter fragments was measured and compared by luciferase activity in the transfected cells. Results: Three clones with size of 1kb, 3kb and 6kb were obtained from mouse genomic DNA. Flow cytometry analysis of JAWSII cells revealed that 52% of the cells expressed CD11c, which was confirmed by RT-PCR analysis. On the contrary, L929 and DC 2.4 cells did not express CD11c. The CD11c+ JAWSII cells were enriched from 52% to 90% with cell sorter. The comparative luciferase activity analyisis demonstrated that the region responsible for tissue specific expression was contained within -3 kb and the clone with size of 3 kb particularly showed higher luciferase activity than 6 kb and 1 kb clones. Conclusion: The CD11c promoter region containing the region responsible for tissue specificity was successfully cloned and -3 kb region showed the highest activity.

• The Korean Journal of Ecology
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• 제15권2호
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• pp.137-145
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• 1992

When exposed to 1, 700 ml of 0.089, 0.445 or 0.890 mM/l cadmius solution, dock (rumex crispus L)plants from heavily polluted chungrangchon site absorbed 0.0404, 0.2244 or 0.4929 mM of cadmium per g dw during the first 4 hours, which were 5.0~30.8 times faster uptake rate than those of water hyacinth (eichhornia crassipes Solm. - laub). Zinc, with which cadmium generally occurs together, did not affect the uptake rate in the concentration range of 0.0306 ~0.0918 mM/l. rumex cripus from chungrangchon site and from less polluted shingalchon site, when exposed to 1, 700 ml of 0.089 mM/l solution for 3 days, removed 68.4% and 63.2%, repectively, of the cadmium initially present in the solution. And when exposed to cadmium solution of the same concentration for the second time after cadmium-free hydroponic culture for three days, these plants removed 76.1% and 66.8% of cadmium, respectively. These removal rates were not significantly different between collection sites or between exposures, but were about 2 times greater for the first exposure, and 2~5 times greater for the second exposure, than those of water hyacinth. these results incate that rumex cripus can absorb, and thus remove, large amount of cadmium ion in wastewater, and so can be used in wastewater treatment, e.g. soil trench method. since there was large difference among the plants in the ability to absorb cadmium, it should be possible to select for strain with greater ability.

• 한국토양비료학회지
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• 제33권1호
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• pp.32-39
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• 2000

하수 오니에 의한 Cd 의 흡착반응을 조사하기 위하여, Cd의 처리농도 (5, 10, 15, 20, 25 및 $50{\mu}g\;Cd\;ml^{-1}$를 달리하여 흡착실험을 수행하였으며, 반응시간 (흡착 반응 후 0.5, 1.0, 1.5, 2.5, 4.5, 6.6, 8.5, 12.5, 24.5 및 48.5 h) 별로 Cd 의 농도를 구하여 흡착반응의 속도상수를 계산하였다. 모든 처리 농도에서 처음 반응시간 30분 이내에 처리 한 Cd의 약 95% 가 흡착되었다. 초기의 빠른 1단계 Cd 흡착반응 후에는 1차 가역 반응식으로 기술할 수 있는 1단계 반응보다는 느린 2단계의 Cd 흡착 반응이 일어났다. 1차 가역 반응식으로 기술할 수 있는 2단계의 Cd 흡착 반응의 속도상수는 $-0.137{\sim}-0.521h^{-1}$의 범위로서 Cd처리 농도가 증가할수록 속도상수는 감소하였다. 흡착 반응에서 평형에 도달하는 시간 (약 6-24 h) 이나, 평형에서의 Cd 의 흡착량 (약 $276-2720{\mu}g\;g^{-1}$) 또는 흡착되지 않고 용액에 남아있는 Cd의 농도 (약 $60-400{\mu}g\;L^{-1}$) 도 Cd 의 처리 농도에 의하여 결정되었다. 즉 Cd 의 처리 농도가 증가할수록 평형에 도달하는 시간, 흡착량 및 평형 농도는 증가하였다. 하수 오니에 의하여 흡착된 Cd 의 일부는 시간이 경과함에 따라 하수 오니로 부터 방출되었으나 그 양은 전체 Cd 흡착량에 비하면 매우 적었다.