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- 검색키워드
- 저자 : Dohyeong Kwon (검색결과 11 건)
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Kwon, Dohyeong,Cha, Bong Geun,Cho, Yuri,Min, Jiyoun,Park, Eun-Byeol,Kang, Suk-Jo,Kim, Jaeyun American Chemical Society 2017 NANO LETTERS Vol.17 No.5
<P>Over the past decade, mesoporous silica nanoparticles (MSNs) smaller than 200 nm with a high colloidal stability have been extensively studied, for systemic drug delivery. Although small molecule delivery via MSNs has been successful, the encapsulation of large therapeutic biomolecules, such as proteins or DNA, is limited due to small pore size of the conventional MSNs obtained by soft-templating. Here; we report the synthesis of mesoporous silica nanoparticles with extra-large pores (XL-MSNs) and their application to in vivo cytokine delivery for Macrophage polarization: Uniform, size-controllable XL-MSNs with 30 nth extra-large pores were synthesized using organic additives and inorganic seed nanoparticles. XL-MSNs showed significantly higher loadings for the model proteins with different molecular weights compared to conventional small pore MSNs. XL-MSNs were used to deliver IL-4, which is an M2-polarizing, cytokine and very quickly degraded in vivo, to macrophages and polarize them to anti-inflammatory M2 macrophages in vivo. XL-MSNs induced a low level of reactive oxygen species (ROS) production and no pro-inflammatory cytokines in bone marrow-derived macrophages (BMDMs) and in mice injected intravenously with XL-MSNs. We found that the injected XL-MSNs were targeted to phagocytic myeloid cells, such as neutrophils, monocytes, macrophages, and dendritic cells. Finally, we demonstrated that the injection of IL-4-loaded XL-MSNs successfully triggered M2 macrophage polarization in vivo, suggesting the clinical potential of XL-MSNs for modulating immune systems via targeted delivery of various cytokines.</P>
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Intracellular calcium is a rheostat for the STING signaling pathway
Kwon, Dohyeong,Sesaki, Hiromi,Kang, Suk-Jo Elsevier 2018 Biochemical and biophysical research communication Vol.500 No.2
<P><B>Abstract</B></P> <P>Stimulator of IFN genes (STING) is essential for the DNA-sensing innate immune pathway. Recently, evidence is emerging that suggests STING also plays important roles in autoimmunity, cancer therapy, and senescence. Although a multitude of post-translational modifications that regulate the STING pathway have been discovered, the cellular events that guide STING translocation remain unclear. Here, we show, paradoxically, that both BAPTA-AM-mediated calcium depletion and ionomycin-induced calcium elevation suppress STING translocation and STING-mediated IFN-β production. We demonstrate that the mitochondria fission mediator DRP1 is crucial for ionomycin-induced inhibition of IFN-β production. Furthermore, knockout of DRP1 suppressed ionomycin-induced increases in calcium as well as mitochondrial fragmentation. Collectively, our findings reveal that the induction of STING signaling is contingent on a fine-tuning of intracellular calcium levels.</P> <P><B>Highlights</B></P> <P> <UL> <LI> BAPTA-AM treatment inhibits the STING translocation and its downstream signaling. </LI> <LI> Ionomycin treatment suppresses the STING translocation and signaling through the influx of extracellular calcium. </LI> <LI> Knockout of DRP1, the mitochondrial fission mediator, hinders the ionomycin-mediated inhibition of STING activity. </LI> <LI> DRP1 regulates ionomycin-induced elevation of intracellular calcium levels. </LI> </UL> </P>
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Kwon, Dohyeong,Park, Eunbyeol,Sesaki, Hiromi,Kang, Suk-Jo Academic Press 2017 Biochemical and biophysical research communication Vol. No.
<P><B>Abstract</B></P> <P>Besides its important role in innate immune response to DNA virus infection, the regulatory function of STING in autoimmunity and cancer is emerging. Recently, multiple mechanisms regulating the activity of the STING pathway have been revealed. Previous study showed that carbonyl cyanide 3-chlorophenylhydrazone (CCCP), the protonophore, inhibited STING-mediated IFN-β production via disrupting mitochondrial membrane potential (MMP). However, how MMP dissipation leads to the suppression of the STING pathway remains unknown. Here, we show that CCCP inhibits activation of STING and its downstream signaling molecules, TBK1 and IRF3, but not STING translocation to the perinuclear region. We found that CCCP impairs the interaction between STING and TBK1 and concomitantly triggers mitochondria fission. Importantly, the knockout of the crucial mitochondria fission regulator Drp1 restored the STING activity, indicating that CCCP down-modulates the STING pathway through DRP1-mediated mitochondria fragmentation. Our findings highlight the coupling of the STING signaling platform to mitochondria dynamics.</P> <P><B>Highlights</B></P> <P> <UL> <LI> CCCP inhibits IFN-β production induced by various types of the STING pathway activators. </LI> <LI> CCCP suppresses the phosphorylation of STING, TBK1, and IRF3 via disrupting the association of STING and TBK1. </LI> <LI> The mitochondria fission mediator DRP1 is essential for CCCP-induced suppression of the STING pathway. </LI> </UL> </P>
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Kwon, Dohyeong,Park, Eunbyeol,Kang, Suk-Jo The Federation of American Societies for Experimen 2017 The FASEB Journal Vol.31 No.11
<P>The stimulator of IFN genes (STING)-mediated DNA-sensing pathway plays an important role in the innate immune response to pathogen infection, autoimmunity, and cancer; however, its regulatory mechanism has not been fully elucidated, and we do not yet know whether the STING pathway is counter-regulated by other innate immune pathways. Here, we show that the NLRP3-activating agonists, ATP and nigericin, prevent STING pathway activation in association with mitochondrial fragmentation; however, the suppression of the STING pathway and mitochondria fission were not dependent on NLRP3 or potassium efflux. Although nigericin-induced mitochondria fission was rescued by knockdown of either dynamin-related protein 1 or TBC1 domain family member 15 (TBC1D15), which are two distinct mitochondria fission regulators, only TBC1D15 restored the activity of the STING pathway, which indicates that inflammasome-activating signals curtail STING pathway activation via TBC1D15. Finally, we found that deficiency of mitofusin (MFN) 1, a mediator of mitochondrial fusion, inhibited STING pathway activation, which leads to a decrease in the induction of IFN-beta and its inducible gene, ISG56, in conjunction with diminished activation of the signaling molecules, TANK-binding kinase 1 and IFN regulatory factor 3, that are downstream of STING. These results highlight the crucial role of MFN1 in maintaining the competency of the STING pathway. Collectively, our findings reveal that mitochondrial dynamics regulators modulate the activation of the STING signaling pathway.</P>
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고영림,Woong Jung,Dohyeong Kwon,김정환 한국식품과학회 2010 Food Science and Biotechnology Vol.19 No.3
There were some reports that the pomegranate juice, seeds, and peel extracts contain steroid hormones including estrone, but the results were controversial. This study was performed to identify estrone in pomegranate extracts through a more sensitive and validated technology. Separation and determination of estrone was carried out using high performance liquid chromatography (HPLC)system with triple quadrupole mass spectrometry. Low concentration of estrone (4.5±0.38 ng/mL) was detected in pomegranate extracts with adequate precision value. The amount of estrone in pomegranate extracts was calculated as 16.4, 18.2, and 20.2 ng/mL, respectively, adjusted by extraction efficiency (average 25.6%) in the precision verification.
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Abdul Basit,조민국,Eui-Yun Kim,Dohyeong Kwon,Suk-Jo Kang,Jae-Ho Lee 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-
Chromosomal instability (CIN) in cancer cells has been reported to activate the cGAS–STING innate immunity pathway via micronuclei formation, thus affecting tumor immunity and tumor progression. However, adverse effects of the cGAS/STING pathway as they relate to CIN have not yet been investigated. We addressed this issue using knockdown and add-back approaches to analyze each component of the cGAS/STING/TBK1/IRF3 pathway, and we monitored the extent of CIN by measuring micronuclei formation after release from nocodazole-induced mitotic arrest. Interestingly, knockdown of cGAS (cyclic GMP-AMP synthase) along with induction of mitotic arrest in HeLa and U2OS cancer cells clearly resulted in increased micronuclei formation and chromosome missegregation. Knockdown of STING (stimulator of interferon genes), TBK1 (TANK-binding kinase-1), or IRF3 (interferon regulatory factor-3) also resulted in increased micronuclei formation. Moreover, transfection with cGAMP, the product of cGAS enzymatic activity, as well as addback of cGAS WT (but not catalytic-dead mutant cGAS), or WT or constitutively active STING (but not an inactive STING mutant) rescued the micronuclei phenotype, demonstrating that all components of the cGAS/STING/TBK1/IRF3 pathway play a role in preventing CIN. Moreover, p21 levels were decreased in cGAS-, STING-, TBK1-, and IRF3knockdown cells, which was accompanied by the precocious G2/M transition of cells and the enhanced micronuclei phenotype. Overexpression of p21 or inhibition of CDK1 in cGAS-depleted cells reduced micronuclei formation and abrogated the precocious G2/M transition, indicating that the decrease in p21 and the subsequent precocious G2/M transition is the main mechanism underlying the induction of CIN through disruption of cGAS/STING signaling.
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Remediation of heavy metal-contaminated soils using eco-friendly nano-scale chelators
Lim, Heejun,Park, Sungyoon,Yang, Jun Won,Cho, Wooyoun,Lim, Yejee,Park, Young Goo,Kwon, Dohyeong,Kim, Han S. Techno-Press 2018 Membrane water treatment Vol.9 No.3
Soil washing is one of the most frequently used remediation technologies for heavy metal-contaminated soils. Inorganic and organic acids and chelating agents that can enhance the removal of heavy metals from contaminated soils have been employed as soil washing agents. However, the toxicity, low removal efficiency and high cost of these chemicals limit their use. Given that humic substance (HS) can effectively chelate heavy metals, the development of an eco-friendly, performance-efficient and cost-effective soil washing agent using a nano-scale chelator composed of HS was examined in this study. Copper (Cu) and lead (Pb) were selected as target heavy metals. In soil washing experiments, HS concentration, pH, soil:washing solution ratio and extraction time were evaluated with regard to washing efficiency and the chelation effect. The highest removal rates by soil washing (69% for Cu and 56% for Pb) were achieved at an HS concentration of 1,000 mg/L and soil:washing solution ratio of 1:25. Washing with HS was found to be effective when the pH value was higher than 8, which can be attributed to the increased chelation effect between HS and heavy metals at the high pH range. In contrast, the washing efficiency decreased markedly in the low pH range due to HS precipitation. The chelation capacities for Cu and Pb in the aqueous phase were determined to be 0.547mmol-Cu/g-HS and 0.192mmol-Pb/g-HS, respectively.
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