• IMMUNE NETWORK
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• 제10권5호
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• pp.153-163
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• 2010

Background: In addition to TCR and costimulatory signals, cytokine signals are required for the differentiation of activated CD8 T cells into memory T cells and their survival. Previously, we have shown that IL-12 priming during initial antigenic stimulation significantly enhanced the survival of activated CD8 T cells and increased the memory cell population. In the present study, we analyzed the mechanisms by which IL-12 priming contributes to activation and survival of CD8 T cells. Methods: We observed dramatically decreased expression of CD43 in activated CD8 T cells by IL-12 priming. We purified $CD43^{lo}$ and $CD43^{hi}$ cells after IL-12 priming and analyzed the function and survival of each population both in vivo and in vitro. Results: Compared to $CD43^{hi}$ effector cells, $CD43^{lo}$ effector CD8 T cells exhibited reduced cytolytic activity and lower granzyme B expression but showed increased survival. $CD43^{lo}$ effector CD8 T cells also showed increased in vivo expansion after adoptive transfer and antigen challenge. The enhanced survival of $CD43^{lo}$ CD8 T cells was also partly associated with CD62L expression. Conclusion: We suggest that CD43 expression regulated by IL-12 priming plays an important role in differentiation and survival of CD8 T cells.

• Molecules and Cells
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• 제41권6호
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• pp.582-590
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• 2018

Endothelial progenitor cells (EPCs) and outgrowth endothelial cells (OECs) play a pivotal role in vascular regeneration in ischemic tissues; however, their therapeutic application in clinical settings is limited due to the low quality and quantity of patient-derived circulating EPCs. To solve this problem, we evaluated whether three priming small molecules (tauroursodeoxycholic acid, fucoidan, and oleuropein) could enhance the angiogenic potential of EPCs. Such enhancement would promote the cellular bioactivities and help to develop functionally improved EPC therapeutics for ischemic diseases by accelerating the priming effect of the defined physiological molecules. We found that preconditioning of each of the three small molecules significantly induced the differentiation potential of $CD34^+$ stem cells into EPC lineage cells. Notably, long-term priming of OECs with the three chemical cocktail (OEC-3C) increased the proliferation potential of EPCs via ERK activation. The migration, invasion, and tube-forming capacities were also significantly enhanced in OEC-3Cs compared with unprimed OECs. Further, the cell survival ratio was dramatically increased in OEC-3Cs against $H_2O_2$-induced oxidative stress via the augmented expression of Bcl-2, a pro-survival protein. In conclusion, we identified three small molecules for enhancing the bioactivities of ex vivo-expanded OECs for vascular repair. Long-term 3C priming might be a promising methodology for EPC-based therapy against ischemic diseases.

• IMMUNE NETWORK
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• 제3권2호
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• pp.110-117
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• 2003

Background: The usefulness of DNA vaccine at priming step of heterologous prime-boost vaccination led to DNA vaccine closer to practical reality. DNA vaccine priming followed by recombinant viral vector boosting via systemic route induces optimal systemic immunity but no mucosal immunity. Mucosal vaccination of the reversed protocol (recombinant viral vector priming-DNA vaccine boosting), however, can induce both maximal mucosal and systemic immunity. Here, we tried to address the reason why the mucosal protocol of prime-boost vaccination differs from that of systemic vaccination. Methods: To address the importance of primary immunity induced at priming step, mice were primed with different doses of DNA vaccine or coadministration of DNA vaccine plus mucosal adjuvant, and immunity including serum IgG and mucosal IgA was then determined following boosting with recombinant viral vector. Next, to assess influence of humoral pre-existing immunity on boosting $CD8^+$ T cell-mediated immunity, $CD8^+$ T cell-mediated immunity in B cell-deficient (${\mu}K/O$) mice immunized with prime-boost regimens was evaluated by CTL assay and $IFN-{\gamma}$-producing cells. Results: Immunity primed with recombinant viral vector was effectively boosted with DNA vaccine even 60 days later. In particular, animals primed by increasing doses of DNA vaccine or incorporating an adjuvant at priming step and boosted by recombinant viral vector elicited comparable responses to recombinant viral vector primed-DNA vaccine boosted group. Humoral pre-existing immunity was also unlikely to interfere the boosting effect of $CD8^+$ T cell-mediated immunity by recombinant viral vector. Conclusion: This report provides the important point that optimally primed responses should be considered in mucosal immunization of heterologous prime-boost regimens for inducing the effective boosting at both mucosal and systemic sites.

• Molecules and Cells
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• 제37권4호
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• pp.286-294
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• 2014

Mammalian polo-like kinase 1 (Plk1) has been studied intensively as a key regulator of various cell cycle events that are critical for proper M-phase progression. The polobox domain (PBD) present in Plk1's C-terminal noncatalytic region has been shown to play a central role in targeting the N-terminal kinase domain of Plk1 to specific subcellular locations. Subsequent studies reveal that PBD binds to a phosphorylated motif generated by one of the two mechanisms - self-priming by Plk1 itself or non-self-priming by a Pro-directed kinase, such as Cdc2. Here, we comparatively review the differences in the biochemical steps of these mechanisms and discuss their physiological significance. Considering the diverse functions of Plk1 during the cell cycle, a better understanding of how the catalytic activity of Plk1 functions in concert with its cisacting PBD and how this coordinated process is intricately regulated to promote Plk1 functions will be important for providing new insights into different mechanisms underlying various Plk1-mediated biological events that occur at the multiple stages of the cell cycle.

• IMMUNE NETWORK
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• 제11권5호
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• pp.268-280
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• 2011

Background: Dengue virus, which belongs to the Flavivirus genus of the Flaviviridae family, causes fatal dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) with infection risk of 2.5 billion people worldwide. However, approved vaccines are still not available. Here, we explored the immune responses induced by alternating prime-boost vaccination using DNA vaccine, adenovirus, and vaccinia virus expressing E protein of dengue virus type 2 (DenV2). Methods: Following immunization with DNA vaccine (pDE), adenovirus (rAd-E), and/or vaccinia virus (VV-E) expressing E protein, E protein-specific IgG and its isotypes were determined by conventional ELISA. Intracellular CD154 and cytokine staining was used for enumerating CD4+ T cells specific for E protein. E protein-specific CD8+ T cell responses were evaluated by in vivo CTL killing activity and intracellular IFN-${\gamma}$ staining. Results: Among three constructs, VV-E induced the most potent IgG responses, Th1-type cytokine production by stimulated CD4+ T cells, and the CD8+ T cell response. Furthermore, when the three constructs were used for alternating prime-boost vaccination, the results revealed a different pattern of CD4+ and CD8+ T cell responses. i) Priming with VV-E induced higher E-specific IgG level but it was decreased rapidly. ii) Strong CD8+ T cell responses specific for E protein were induced when VV-E was used for the priming step, and such CD8+ T cell responses were significantly boosted with pDE. iii) Priming with rAd-E induced stronger CD4+ T cell responses which subsequently boosted with pDE to a greater extent than VV-E and rAd-E. Conclusion: These results indicate that priming with live viral vector vaccines could induce different patterns of E protein-specific CD4+ and CD8+ T cell responses which were significantly enhanced by booster vaccination with the DNA vaccine. Therefore, our observation will provide valuable information for the establishment of optimal prime-boost vaccination against DenV.

• 조명전기설비학회논문지
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• 제15권6호
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• pp.1-7
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• 2001

플라즈마 디스플레이의 구동원리를 해석하기 위하여 공간전하가 방전특성에 미치는 영향을 연구하였다. 프라이밍(priming) 방전에 의해 발생된 공간전하는 다음 방전의 방전지연시간을 단축시켜 응답속도를 빠르게 한다. 이러한 영향은 프라이밍 방전 이후 30[$\mu\textrm{s}$] 정도까지 유효하다. 이 공간전하는 프라이밍 셀 인근의 방전개시전압 을 저하시키고 바로 옆의 셀의 방전에 가장 크게 그 영향을 미친다. 그리고 방전 펄스 폭이 좁을수록 방전개시전압 강하 폭이 커지므로 공간전하에 대한 의존도가 강하다. 그러나 펄스 폭 1[$\mu\textrm{s}$] 이상에서는 공간전하에 대한 영향이 매우 미약하게 관측되었다. 그러므로 인접한 방전의 공간전하에 대해 영향을 받지 않고 안정적인 방전이 일어나기 위해서 최소한 펄스 폭이 1[$\mu\textrm{s}$] 이상 되어야 함을 알았다.

• Biomolecules & Therapeutics
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• 제29권3호
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• pp.295-302
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• 2021

Microglial priming is the process of microglial proliferation and activation in response to neurodegeneration and abnormal protein accumulation. Priming makes microglia susceptible to secondary inflammatory stimuli and causes exaggerated inflammatory responses. In the present study, we established a microglial priming model in mice by administering a single injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg). MPTP induced microglial activation without dopaminergic degeneration; however, subsequent treatment with a sub-toxic dose of lipopolysaccharides (LPS) induced an amplified inflammatory response and caused nigrostriatal dopaminergic degeneration. These pathological and inflammatory changes, including microglial activation and dopaminergic cell loss in the substantia nigra (SN) area were reversed by papaverine (PAP) administration. In addition, MPTP/LPS enhanced interleukin-1β (IL-1β) expression and processing via nod-like receptor protein 3 (NLRP3) inflammasome activation in the SN region of mice. However, PAP treatment suppressed inflammasome activation and subsequent IL-1β maturation. Moreover, PAP inhibited nuclear factor-κB (NF-κB) and enhanced cAMP-response element binding protein (CREB) activity in the SN of MPTP/LPS mice. These results suggest that PAP inhibits the activation of NLRP3 inflammasome by modulating NF-κB and CREB signaling pathways, which results in reduced microglial activation and neuronal cell death. Thus, PAP may be a potential candidate for the treatment of Parkinsons's disease, which is aggravated by systemic inflammation.

• 생물환경조절학회지
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• 제12권4호
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• pp.221-227
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• 2003

본 연구에서는 토마토 종자의 priming 및 발아과정 중 세포막의 기능이 종자활력에 미치는 영향을 구명하고자 하였다. 토마토 종자의 적정 priming 처리제는 150 mL의 $KNO_3$였고, priming 처리된 종자는 발아촉진에 유효하였으며, 그 효과는 저온에서 현저하였다. $KNO_3$로 priming은 처리과정중 처리제에서 분리된 이온이 종자내로 이동하였다. Priming 처리과정중 전기전도도는 발아속도 단축에 가장 효과적이었던 $KNO_3$에서 처리개시 직후 약간 낮았다가 그 후 처리최종일까지 일정한 수준을 유지하였다. 발아기간중 용액의 전기전도도는 $KNO_3$ 용액으로 priming 처리된 종자에서는 낮았으나, $K_3PO_4$ 용액으로 priming 종자에서는 높게 나타났다. 발아촉진에 가장 효과적이었던 priming 처리제인 150 mL의 $KNO_3$ 용액으로 priming 처리하면 처리과정중 단백질, 아미노산, 가용성 당의 유출량은 $K_3PO_4$ 및 침지종자에 비해 낮았으며, 그 효과는 발아시에도 유지되었다.

• IMMUNE NETWORK
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• 제13권3호
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• pp.86-93
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• 2013

In the present study, we investigated if priming of autoreactive $CD8^+T$ cells would be inhibited by competitive peptides for major histocompatibility complex (MHC) class I binding. We used a mouse model of vitiligo which is induced by immunization of $K^b$-binding tyrosinase-related protein 2 (TRP2)-180 peptide. Competitive peptides for $K^b$ binding inhibited IFN-${\gamma}$production and proliferation of TRP2-180-specific $CD8^+T$ cells upon ex vivo peptide restimulation, while other MHC class I-binding peptides did not. In mice, the capability of inhibition was influenced by T-cell immunogenicity of the competitive peptides. The competitive peptide with a high T-cell immunogenicity efficiently inhibited priming of TRP2-180-specific $CD8^+T$ cells in vivo, whereas the competitive peptide with a low T-cell immunogenicity did not. Taken together, the inhibition of priming of autoreactive $CD8^+T$ cells depends on not only competition of peptides for MHC class I binding but also competitive peptide-specific $CD8^+T$ cells, suggesting that clonal expansion of autoreactive T cells would be affected by expansion of competitive peptide-specific T cells. This result provides new insights into the development of competitive peptides-based therapy for the treatment of autoimmune diseases.

• The Plant Pathology Journal
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• 제27권3호
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• pp.272-279
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• 2011

Root colonization of Arabidopsis thaliana with Pseudomonas chlororaphis O6 induces systemic tolerance against diverse pathogens, as well as drought and salt stresses. In this study, we demonstrated that 11 genes in the leaves were up-regulated, and 5 genes were down-regulated as the result of three- to five-days root colonization by P. chlororaphis O6. The identified priming genes were involved in cell signaling, transcription, protein synthesis, and degradation. In addition, expression of selected priming genes were induced in P. chlororaphis O6-colonized plants subjected to water withholding. Genes encoding defense proteins in signaling pathways regulated by jasmonic acid and ethylene, such as VSP1 and PDF1.2, were additional genes with enhanced expression in the P. chlororaphis O6-colonized plants. This study indicated that the expression of priming genes, as well as genes involved in jasmonic acid- and ethylene-regulated genes may play an important role in the systemic induction of both abiotic and biotic stress due to root colonization by P. chlororaphis O6.