The Study of a Dendritic Cells-Based Standardized Evaluation System for Immunity-Boosting Functional Foods

Jaeyul Kwon(권재열) 한국식품영양과학회 2020 한국식품영양과학회 학술대회발표집 Vol.2020 No.10

Pathway Enrichment Analysis and Visualization of Transcriptomic Data from BMDC Treated with Fucoidan

Jaeyul Kwon 한국식품영양과학회 2021 한국식품영양과학회 학술대회발표집 Vol.2021 No.10

Fucoidans, sulfated polysaccharides from brown seaweed, possess a variety of biological activities including antiviral, antioxidant, immunoregulatory, and antitumor function. The mechanisms by which fucoidans interact with antigen-presenting cells remain elusive. Herein, we describe the transcriptional programs induced in bone marrow-derived dendritic cells (BMDCs) by fucoidan. Exposure of BMDCs to fucoidan from brown alga Fucus evanescens led to upregulation of 2,376 gene sets in which 728 gene sets are significant at FDR <25%. Gene lists from RNA-seq experiments were interpreted by pathway enrichment analysis and visualization of omics data using g:Profiler, Gene Set Enrichment Analysis (GSEA), Cytoscape, and EnrichmentMap.

Comparative proteomic analysis of plant responses to sound waves in Arabidopsis

Kwon, Young Sang,Jeong, Mi-Jeong,Cha, Jaeyul,Jeong, Sung Woo,Park, Soo-Chul,Shin, Sung Chul,Chung, Woo Sik,Bae, Hanhong,Bae, Dong-Won The Korean Society of Plant Biotechnology 2012 식물생명공학회지 Vol.39 No.4

Environmental factors greatly influence the growth, development, and even genetic characteristics of plants. The mechanisms by which sound influences plant growth, however, remain obscure. Previously, our group reported that several genes were differentially regulated by specific frequenciesof sound treatmentusing a sound-treated subtractive library. In this study, we used a proteomic approach to investigate plant responses to sound waves in Arabidopsis. The plants were exposed to 250-Hz or 500-Hz sound waves, and total proteins were extracted from leaves 8 h and 24 h after treatment. Proteins extracted from leaves were subjected to 2-DE analysis. Thirty-eight spots were found to be differentially regulated in response to sound waves and were identified using MALDI-TOF MS and MALDI-TOF/TOF MS. The functions of the identified proteins were classified into photosynthesis, stress and defense, nitrogen metabolism, and carbohydrate metabolism. To the best of our knowledge, this is the first report on the analysis of protein changes in response to sound waves in Arabidopsis leaves. These findings provide a better understanding of the molecular basis of responses to sound waves in Arabidopsis.

Lichen-forming fungus<i>Caloplaca flavoruscens</i>inhibits transcription factors and chromatin remodeling system in fungi

Kwon, Youngho,Cha, Jaeyul,Chiang, Jennifer,Tran, Grant,Nislow, Corey,Hur, Jae-Seoun,Kwak, Youn-Sig,Deising, Holger Oxford University Press 2016 FEMS microbiology letters Vol.363 No.12

Reversible Inactivtion of PTEN by superoxide and hydrogen peroxide through a disulfide formation between Cys residues 124 and 71

Lee, Seung-Rock,Yang, Kap-Seok,Kwon, Jaeyul,Lee, Chunghee,Kang, Sangwon,Rhee, Sue Goo 이화여자대학교 세포신호전달연구센터 2001 고사리 세포신호전달 심포지움 Vol. No.3

The tumor suppressor PTEN is a phosphatase that acts 3-phosphorylated phosphoinositides, including PtdIns 3,4,5-P₃ Like protein tyrosine phosphatases, PTEN contains a reactive, essential cysteine, Cys124, at its active site. PTEN plays important roles in the control of apoptosis, cell cycle progression and development by acting in conjunction with PI3K to regulate the levels of PtdIns 3,4,5-P₃ How the activity of PTEN is regulated in response to extracellular stimuli, however, is not known. Overexpression of Mox, a gp91 component of NADPH oxidase or a dominant negative mutant of peroxiredoxin Ⅱ, a H₂O₂ scavenging enzyme resulted in increase in the level of PtdIns 3,4,5-P₃, suggesting that H₂O₂ might modulate intracelluar levels of PtdIns 3,4,5-P₃, by either activating PI3-kinase or inhibiting PTEN or both. We studied PTEN as a target of H₂O₂. Incubation of purified PTEN with H₂O₂ resulted in a manner dependent on time and H₂O₂ concentration. Studies of various Cys mutants and direct mass spectral analysis of tryptic peptides indicated that Cys124 formed a disulfide with Cys71 upon oxidation by H₂O₂ and superoxide anion. The sensitivity of PTEN to H₂O₂ produced in vivo in response to receptor activation was tested in human neutrophils stimulated with fMLP. The amount of oxidized PTEN increased with time of incubation with fMLP, reached a maximum at 5 min, and returned to the basal levels by 20 mm, suggesting that the PTEN oxidation is reversible. Incubation of cells with 1-chloro-2,4-dinitrobenzene, an inhibitor of TrxR, caused the conversion of reduced PTEN to the oxidized form, whereas buthionine sulfoximine, an inhibitor of GSH biosynthesis, did not have any effect. These results suggest that the activity of PTEN is regulated through reversible oxidation by H₂O₂ and that the reduction is achieved mainly by Trx.

TNFα and IL-1β in the synovial fluid facilitate mucosal-associated invariant T (MAIT) cell migration

Kim, Miok,Yoo, Su-Jin,Kang, Seong Wook,Kwon, Jaeyul,Choi, Inpyo,Lee, Chang Hoon Elsevier 2017 Cytokine Vol.99 No.-

<P><B>Abstract</B></P> <P>Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that primarily affect the joints and inflammatory cell migration into inflamed articular sites contribute to this disease. Among the inflammatory cells, human mucosal-associated invariant T (MAIT) cells were recently recognized as critical cellular component with a pathological role in RA. However, their migratory characteristics are poorly understood. The aim of this study was to determine whether human MAIT cells preferentially traffick to inflamed synovial sites in rheumatoid arthritis patients and to elucidate the underlying mechanism. First, we found that TNFα and IL-1β were elevated in synovial fluid (SF) of RA patients, which resulted in increased expression of E-selectin, ICAM-1 and V-CAM-1 on blood vessel endothelial cells. To understand whether TNFα and IL-1β in the SF facilitated MAIT cell migration, we analyzed CD161<SUP>+</SUP> TCRα7.2<SUP>+</SUP> MAIT and other CD3<SUP>+</SUP> T cells for differences in migratory capacity. Collectively, our results demonstrate that TNFα and IL-1β in the SF facilitated MAIT cell migration dependent on expression of selectin ligand, sialyl Lewis<SUP>X</SUP> (sLe<SUP>X</SUP>) and CCR6 on MAIT cells. We also showed that MAIT cells in the SF from RA patients equipped upregulated sLe<SUP>X</SUP> compared to the peripheral blood of RA patients and healthy persons, which suggest that TNFα and IL-1β mediated expression of E-selectin preferentially attract sLe<SUP>X</SUP> mediated MAIT cell migration into the SF of RA patients.</P>

A Novel Substrate of Mammalian Thioredoxin Reductase 1

Jeong, Woojin,Yoon, Hae Won,Kim, Jae-Ryong,Kwon, Ki-Sun,Lee, Seung-Rock,Kwon, Jaeyul,Rhee, Sue Goo 이화여자대학교 세포신호전달연구센터 2001 고사리 세포신호전달 심포지움 Vol. No.3

Recent evidence suggests that a number of proteins are oxidized at their critical cysteine residues as the result of receptor-mediated H₂O₂ production. At the present time, the reduction of these oxidized proteins is thought to be achieved by general electron suppliers such as Trx, Grx and GSH. Evidence(e.g., Trx reduces oxidized Prx Ⅰ-Ⅴ enzymes but not oxidized Prx Ⅵ; Trx, but not Grx or GSH, reduces oxidized PTP1B), however, suggests that the reduction reaction might be governed by specific interactions between the donor and acceptor molecules. Signal transduction paradigms instruct us that both modification and demodification of proteins are controlled processes. As such, we searched new electron donor molecules and found several small proteins containing a CysXXCys(or CysXXSeCys) motif, which is conserved among the members of the thiol-disulfide oxidoreductase superfamily that includes Trx and Grx. One of these is a 14-kDa protein, which we named Trx-related protein 14(TRP14). Its overall similarity to Trx is low(<20%). The homology search showed that TRP14 homologs exist in a wide range of organisms from bacteria to mammals. Immunoblot analysis indicates that TRP14 is a ubiquitous protein like Trx. TRP14 was expressed at much lower levels than Trx in every tissue examined except in kidney. The reduction potentials were similar for TRP14(-0.257V) and Trx(-0.274V). Studies with mutant proteins in which the two conserved cysteine residues(Cys43 and Cys46) were altered and direct analysis of the Cys-containing peptides revealed that, as in the case of Trx, the conserved cysteine residues form an intramolecular disulfide linkage upon oxidation by hydrogen peroxide. The resulting disulfide could be reduced by TrxR1 but not by TrxR2, whereas Trx is an equally good substrate for TrxR1 and TrxR2. For the reduction reaction by TrxR1, TRP14 was a better substrate than Trx. Trx serves as a hydrogen donor for the catalytic function of ribonucleotide reductase, methionine sulfoxide reductase, and peroxiredoxins. TRP14 could not support any of these three reactions. This substrate specificity, although surprising in view of their similar reduction potentials, suggests that specific protein-protein interactions or the pKa values of the conserved cysteine residues, in addition to reduction potential, may govern the electron flows from Trx and Trx-like proteins to acceptor proteins. To search for proteins that depend on TRP14 for the supply of reducing equivalents, GST-TRP14 fusion protein was immobilized to Sepharose gels. TrxR1 was found to bind specifically to the TRP14-bound Sepharose column. Our results suggest that TRP14 is a disulfide-oxidoreductase that is capable of receiving electrons from NADPH via TrxR1. The downstream targets of TRP14 in the reduction cascade remain to be identified.

Roles of Reactive Oxygen Species in Rheumatoid Arthritis Pathogenesis

( Su-jin Yoo ),( Eunbyeol Go ),( Ye-eun Kim ),( Sunyoung Lee ),( Jaeyul Kwon ) 대한류마티스학회 2016 대한류마티스학회지 Vol.23 No.6

Rheumatoid arthritis (RA) is an autoimmune disease that starts with decreased tolerance to modified self-antigens and even-tually leads to synovitis and destruction of bone and cartilage. Age is a risk factor for developing RA. Major changes in the im-mune system come with age due to chronic oxidative stress on the deoxyribonucleic acid (DNA) damage pathway, somatic mu-tation, modifications of auto-antigens, T cell tolerance and activation of fibroblast-like synoviocytes (FLS). Reactive oxygen spe-cies (ROS) generated by nicotinamide adenine dinucleotide phosphate oxidase 2 (NADPH oxidase 2) suppress T cell receptor signaling. Sirtuin 1 (SIRT1) is a critical immune suppressor of T cell activation and a key regulator of oxidative stress. When oxi-dative stress reduces activity of SIRT1, the breakdown of tolerance to modified self-antigens is expected. Generation of ROS can be perpetuated by enhanced DNA damage and dysfunctional mitochondria in a feedback loop during the development of RA. Through major T cell loss and selective proliferation of peripheral T cells, pro-inflammatory T cell pools with abnormal features are established in the T cell compartment. Hypoxic and inflammatory condition in synovium perpetuates ROS generation, which leads to the activation of FLS. In both T cell and synovium compartment, oxidative stress reshapes the immune system into the development of pre-clinical RA. (J Rheum Dis 2016;23:340-347)

Roles of Reactive Oxygen Species in Rheumatoid Arthritis Pathogenesis

Yoo, Su-Jin,Go, Eunbyeol,Kim, Ye-Eun,Lee, Sunyoung,Kwon, Jaeyul 대한류마티스학회 2016 대한류마티스학회지 Vol.14 No.1

장의 급성 이식편대숙주병에서 대변미생물무리이식을 시행한 2예

연상훈 ( Sang Hoon Yeon ),이명원 ( Myung-won Lee ),조덕연 ( Deog-Yeon Jo ),허부연 ( Bu-Yeon Heo ),권재열 ( Jaeyul Kwon ),송익찬 ( Ik-Chan Song ) 대한내과학회 2021 대한내과학회지 Vol.96 No.4

급성 이식편대숙주병은 동종 조혈모세포이식의 비-재발(non-relapse) 사망률과 연관되어 있는 중요한 합병증 중 하나이다. 대변미생물무리이식을 통해 장의 미생물무리를 복원함으로써 장의 이식편대숙주병을 치료하려는 노력이 시도되고 있다. 저자들은 장의 스테로이드 불응 이식편대숙주병이 있는 환자 2명에게 대변미생물무리이식을 시행한 경험을 문헌고찰과 함께 보고하고자 한다. 첫 번째 증례는 43세 남자로 형제로부터 동종 조혈모세포이식을 받았고, 두 번째는 70세 여자로 아들로부터 사람백혈구항원 반일치 조혈모세포이식을 받았다. 두 환자는 각각 이식 후 7주 및 4주째에 급성 이식편대숙주병이 장에 발생하였다. 두 환자 모두에서 조혈모세포이식의 공여자로부터 대변을 제공받아 대변미생물무리이식을 시행하였다. 이후, 두 환자 모두에서 임상적인 증상의 호전을 보였으며, 첫 번째 환자는 완전 반응을, 두 번째 환자에서는 부분 반응을 보였다. RNA 염기서열 분석을 통해 대변미생물무리이식 전과 후의 대변을 분석하였을 때 대변 미생물무리이식 후 미생물무리의 다양성이 회복되는 것이 관찰되었다. 이로써 동종 조혈모세포이식 후에 발생하는 장의 스테로이드 불응-급성 이식편대숙주병의 치료 방법으로 대변미생물무리이식을 적극적으로 고려해야 하겠다. Restoring the microbiota via fecal microbiota transplantation (FMT) can be an effective treatment for steroid-refractory acute graft-versus-host disease (GVHD) of the gut. Here, we report two adult patients who underwent FMT to treat steroid-refractory acute GVHD of the gut. The first patient was a 43-year-old man who underwent allogeneic hematopoietic stem cell transplantation (HSCT) with cells from a matched sibling donor. The second patient was a 70-year-old woman who underwent haplo-identical HSCT with cells from her son. Gut GVHD developed at 7 and 4 weeks after HSCT, respectively. After undergoing FMT, the clinical symptoms improved; the first patient had a complete response and the second patient had a partial response. Microbial analyses using RNA gene sequencing showed that a diverse fecal microbiome was recovered by 4 weeks after FMT. FMT should be considered an effective therapeutic option for managing steroid-refractory acute GVHD of the gut. (Korean J Med 2021;96:358-362)