Triple costimulation via CD80, 4-1BB, and CD83 ligand elicits the long-term growth of Vγ9Vδ2 T cells in low levels of IL-2

Cho, Hyun-Woo,Kim, Su-Yeon,Sohn, Dae-Hee,Lee, Min-Ji,Park, Mi-Young,Sohn, Hyun-Jung,Cho, Hyun-Il,Kim, Tai-Gyu Federation of American Societies for Experimental 2016 Journal of Leukocyte Biology Vol.99 No.4

<P>Human gamma delta T cells play important roles in the regulation of infection and cancer. To understand the roles of costimulatory signals in activation and expansion ex vivo, V gamma 9V delta 2 T cells were grown with artificial APCs that express CD83, 4-1BB ligand, and/or CD32, which allowed a loading of alpha CD3 and alpha CD28 antibodies. The costimulatory signals through CD80, 4-1BB, and CD83 ligand in low levels of IL-2 triggered an explosive ex vivo proliferation of V gamma 9V delta 2 T cells capable of secreting high levels of IL-2, IFN-gamma, and TNF-alpha. Moreover, the triple-costimulatory signals cause augmented cell viabilities for long-term growth of V gamma 9V delta 2 T cells, resulting in phenotypic changes to CD272(-)CD45RA(+) effector memory-like cells. Notably, we observed that CD83 ligand signaling is crucial to promote ex vivo expansion, survival, and cytolytic effector functions of V gamma 9V delta 2 T cells. In contrast, 4-1BB signaling is moderately important in up-regulating surface molecules on V gamma 9V delta 2 T cells. Consequently, gd T cells stimulated in the presence of triple-costimulatory signals have diverse cytolytic effector molecules, including perforin, granzyme A, granzyme B, and Fas ligand, eliciting potent cytolytic activities against tumor cells. Overall, our results provide insights into the roles of costimulatory signals in manufacturing long-lived and fully functional V gamma 9V delta 2 T cells that could be useful against cancers.</P>

Caffeic acid phenethyl ester promotes anti-inflammatory effects by inhibiting MAPK and NF-κB signaling in activated HMC-1 human mast cells

Cho, Mi Suk,Park, Won Sun,Jung, Won-Kyo,Qian, Zhong-ji,Lee, Dae-Sung,Choi, Jung-Sik,Lee, Da-Young,Park, Sae-Gwang,Seo, Su-Kil,Kim, Hak-Ju,Won, Jun Yeon,Yu, Byeng Chul,Choi, Il-Whan Informa Healthcare USA, Inc. 2014 PHARMACEUTICAL BIOLOGY Vol.52 No.7

<P><I>Context</I>: Caffeic acid phenethyl ester (CAPE), an active component of honeybee propolis, is known to have antioxidant, anti-inflammatory, and other beneficial medicinal properties. However, the molecular mechanisms underlying its anti-allergic effects in mast cells are unknown.</P><P><I>Objective</I>: The purpose of the present study was to examine whether CAPE modulates the immunoglobulin E (IgE)-mediated local allergic reaction in animals, as well as to elucidate the effects of CAPE on mast cells <I>in vitro</I>.</P><P><I>Materials and methods</I>: To investigate the bioactive potential of CAPE (10 or 20 µM), HMC-1 cells were stimulated with phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI) for 24 h in the presence or absence of CAPE. To study the pharmacological effects of CAPE, enzyme-linked immunosorbent assays (ELISAs), RT-PCR, Western blot analysis, electrophoretic mobility shift assays (EMSAs), and fluorescence assays were used.</P><P><I>Results</I>: CAPE (10 mg/kg) inhibited local IgE-mediated allergic reactions (0.164 versus 0.065 O.D.) in a mouse model. Additionally, CAPE (20 µM) attenuated PMACI-stimulated histamine release (3146.42 versus 2564.83 pg/ml) and the production of inflammatory cytokines, such as interleukin (IL)-1β (4.775 versus 0.713 pg/ml, IC<SUB>50</SUB> = 6.67 µM), IL-6 (4771.5 versus 449.1 pg/ml, IC<SUB>50</SUB> = 5.25 µM), and IL-8 (5991.7 versus 2213.1 pg/ml, IC<SUB>50</SUB> = 9.95 µM) in HMC-1 cells. In activated HMC-1 cells, pretreatment with CAPE decreased the phosphorylation of c-Jun N-terminal kinase. In addition, CAPE inhibited PMACI-induced nuclear factor (NF)-κB activation by suppressing IκBα phosphorylation and its degradation.</P><P><I>Discussion and conclusion</I>: Our results indicated that CAPE can modulate mast cell-mediated allergic disease.</P>

Anti-photoaging effect of fermented agricultural by-products on ultraviolet B-irradiated hairless mouse skin

CHOI, SUN-IL,JUNG, TAE-DONG,CHO, BONG-YEON,CHOI, SEUNG-HYUN,SIM, WAN-SUP,HAN, XIONGGAO,LEE, SANG JONG,KIM, YOUNG-CHEUL,LEE, OK-HWAN UNKNOWN 2019 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.44 No.2

<P> Processed products from agricultural produce generate a large number of agricultural by-products that contain a number of functional substances. These are often discarded owing to the lack of suitable processing methods. The present study investigated the anti-photoaging properties of fermented rice bran (FRB), soybean cake (FSB) and sesame seed cake (FSC) on ultraviolet B (UVB)-irradiated hairless mouse skin. Results indicated that the oral administration of FRB, FSB and FSC effectively inhibited the UVB irradiation-induced expression of matrix metalloproteinase (MMP)-2, MMP-9, MMP-3 and MMP-13. Reverse transcription-quantitative polymerase chain reaction results also demonstrated that FRB, FSB and FSC significantly inhibited the UVB-induced expression of the genes encoding tumor necrosis factor-α, inducible nitric oxide synthase, interleukin (IL)-6 and IL-1β when compared with the UVB-vehicle group (P<0.05). Additionally, collagen degradation and mast cell infiltration were reduced in hairless mouse skin. Furthermore, UVB-induced wrinkle formation was also significantly reduced in mouse skin compared with the UVB-vehicle group (P<0.05). These results reveal that fermented agricultural by-products may serve as potential functional materials with anti-photoaging activities. </P>

반복적 관절내 출혈이 관절 활막과 연골 세포의 변화에 미치는 영향

유명철(Myung Chul Yoo),조윤제(Yoon Jae Cho),김강일(Kang Il Kim),전성욱(Sung Wook Chun),소동혁(Dong Hyuk So),조형준(Hyung Jun Cho),양형인(Hyung-In Yang),이상훈(Sang-Hoon Lee),이연아(Yeon-Ahn Lee) 대한정형외과학회 2008 대한정형외과학회지 Vol.43 No.3

목적: 혈액의 관절강내 반복주사 동물 모델을 이용하여, 혈우병성 관절염에서 활막의 변화와 연골 파괴에 대한 병리 기전과 경과 과정을 연구하였다. 대상 및 방법: 뉴질랜드 백색 토끼 수컷 20마리에 18주간 1주 3회씩 귀에서 자가 혈액을 채취하여 우측 슬관절에 1 ㎖를 주사하고, 좌측 슬관절에 생리식염수 1㎖를(대조군) 주사하였다. 11주 후와 18주 후에 양측 슬관절의 X선 촬영을 시행하였고, 활액막과 연골을 채취하여 조직검사를 시행하였다. 활막 세포 배양에서 RT PCR를 이용한 cytokine의 변화를 관찰 하였고, 연골 세포를 추출 배양하여 GAG 및 PGE₂, MMP-1,3 생성을 측정하였다. 결과: 11주째 육안적 변화는 없었으나, 우측 슬관절의 활액막은 조직학적으로 경한 증식반응과 형질세포 및 단핵세포의 활액막내 침착을 보이며 약간의 염증 소견을 나타냈다. 단순 방사선 소견상 특이 소견은 발견되지 않았다. 18주 후에는 육안적으로 우측 슬관절이 좌측에 비하여 부어 있었고, 단순 방사선학적 소견에서는 관절의 퇴행성 변화가 관찰 되었다. 병리학적 소견은 활막의 심한 증식과 염증세포의 침윤이 관찰되었다. 활막의 real-time RT PCR 시행결과 TNF-alpha, IL-1, MMP-1 mRNA 발현이 증가되었다. 연골세포 배양에서 대조군과 비교시 GAG 생성은 감소하고 PGE₂는 증가하였으며 MMP-1과 MMP-3는 변화가 없었다. 결론: 반복적인 관절 내 출혈은 활막세포를 자극하여 활막의 심한 증식과, proinflammatory cytokines의 생성을 증가시키며, 이는 연골 세포의 재생을 억제하고 연골세포의 염증을 증가시켜 연골의 대사기능이 억제되면서 퇴행성 변화를 촉진하여 점차적으로 관절염으로 이행되는 것으로 사료된다. Purpose: We designed this study to demonstrate the pathophysiology of hemophilic arthropathy (HA) by creating an animal model for determining the effect of repeated intraarticular bleeding in the synovium and articular cartilage. Materials and Methods: 20 normal male New Zealand white rabbits were used for this study. We injected 1 ㎖ of autologous blood from the ear vein of the rabbits into the right knee joint three timeds a week for 18 weeks, and we injected 1 ㎖ of normal saline into the left knee joint three times a week for 18 weeks as a control group. We examined the pathologic changes by microscopy and plain X-ray, and we determined the mRNA expression of proinflammatory cytokines in the synovium of the HA by performing real time RT-PCR at the 11<SUP>th</SUP> week and 18<SUP>th</SUP> week after starting blood-injection. We also examined the GAG and the PGE2 production in cultured chondrocytes that were extracted from the HA knees. Results: At the 11<SUP>th</SUP> week, after blood injection there were no remarkable gross changes in the HA knees and the control knee joints. At the 18<SUP>th</SUP> weeks, the experimental knee joints (HA knees) showed grossly swelling and degenerative changes by X-ray. The infiltration of inflammatory cells and the synovial proliferation in the HA knee joints were compared with that in the control knee joints by microscopic examination. The expressions of the mRNA of TNF-alpha, IL-1, MMP-1 and MMP-3 in the HA synovium were increased, as determined by real time RT-PCR, as compared with that in the control knee. In the cultured chondrocytes, the GAG production was decreased and the PGE2 was increased, but the MMP-1 and MMP-3 were not changed, as determined by ELISA. Conclusion: Our results showed that the GAG production of chondrocytes of the HA knees was decreased and there was increased PGE2, so that the cartilage degeneration by intra-articular bleeding was caused by the decreased metabolism of chondrocytes rather than by increased catabolism of the chondrocytes. We suggest that HA was associated with synovitis and cartilage degeneration, but decreased cartilage metabolism was the major mechanism of HA.

Anti-inflammatory Effects of Ethanolic Extracts from Codium fragile on LPS-Stimulated RAW 264.7 Macrophages via Nuclear Factor kappaB Inactivation

Yoon, Ho-Dong,Jeong, Eun-Ji,Choi, Ji-Woong,Lee, Min-Sup,Park, Myoung-Ae,Yoon, Na-Young,Kim, Yeon-Kye,Cho, Deuk-Moon,Kim, Jae-Il,Kim, Hyeung-Rak The Korean Society of Fisheries and Aquatic Scienc 2011 Fisheries and Aquatic Sciences Vol.14 No.4

Bacterial lipopolysaccharide (LPS) induces expression of pro-inflammatory cytokines and enzymes producing nitric oxide (NO) and prostaglandins (PGs) in immune cells. This process is mediated by the activation of nuclear factor kappaB (NF-${\kappa}B$). In this study, we investigated the anti-inflammatory characteristics of Codium fragile ethanolic extract (CFE) mediated by the regulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) using LPS-stimulated murine macrophage RAW 264.7 cells. CFE significantly inhibited LPS-induced NO and $PGE_2$ production in a dose-dependent manner and suppressed the expression of iNOS and COX-2 proteins in LPS-stimulated RAW 264.7 cells with no cytotoxicity. Pro-inflammatory cytokines, such as interleukin (IL)-$1{\beta}$, IL-6, and tumor necrosis factor-${\alpha}$, were significantly reduced by treatment of CFE in LPS-stimulated RAW 264.7 cells. CFE inhibited the promoter activity of (NF)-${\kappa}B$ in LPS-stimulated macrophages. Treatment with CFE suppressed translocation of the NF-${\kappa}B$ p65 subunit by preventing proteolytic degradation of inhibitor of ${\kappa}B-{\alpha}$. These results indicate that the CFE-mediated inhibition of NO and $PGE_2$ production in LPS-stimulated RAW 264.7 cells is mediated through the NF-${\kappa}B$-dependent transcriptional downregulation of iNOS and COX-2, suggesting the potential of CFE as a nutraceutical with anti-inflammatory activity.

Original Articles : Anti-inflammatory Effects of Ethanolic Extracts from Codium fragile on LPS-Stimulated RAW 264.7 Macrophages via Nuclear Factor kappaB Inactivation

( Ho Dong Yoon ),( Eun Ji Jeong ),( Ji Woong Choi ),( Min Sup Lee ),( Myoung Ae Park ),( Na Young Yoon ),( Yeon Kye Kim ),( Deuk Moon Cho ),( Jae Il Kim ),( Hyeung Rak Kim ) 한국수산과학회(구 한국수산학회) 2011 Fisheries and Aquatic Sciences Vol.14 No.4

Bacterial lipopolysaccharide (LPS) induces expression of pro-inflammatory cytokines and enzymes producing nitric oxide (NO) and prostaglandins (PGs) in immune cells. This process is mediated by the activation of nuclear factor kappaB (NF-κB). In this study, we investigated the anti-inflammatory characteristics of Codium fragile ethanolic extract (CFE) mediated by the regulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) using LPS-stimulated murine macrophage RAW 264.7 cells. CFE significantly inhibited LPS-induced NO and PGE2 production in a dose-dependent manner and suppressed the expression of iNOS and COX-2 proteins in LPS-stimulated RAW 264.7 cells with no cytotoxicity. Pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, were significantly reduced by treatment of CFE in LPS-stimulated RAW 264.7 cells. CFE inhibited the promoter activity of (NF)-κB in LPS-stimulated macrophages. Treatment with CFE suppressed translocation of the NF-κB p65 subunit by preventing proteolytic degradation of inhibitor of κB-α. These results indicate that the CFE-mediated inhibition of NO and PGE2 production in LPS-stimulated RAW 264.7 cells is mediated through the NF-κB-dependent transcriptional downregulation of iNOS and COX-2, suggesting the potential of CFE as a nutraceutical with anti-inflammatory activity.

용혈성 빈혈과 흑수열을 동반한 Chloroquine저항성 수입 열대열 말라리아 1예

조희충,국기용,박일,최연수,이승일 조선대학교 1994 The Medical Journal of Chosun University Vol.19 No.1

저자들은 최근 아프리카를 여행하는 도중 말라리아의 예방약제인 chloroquine을 복용하였음에도 불구하고 용혈성 빈혈과 흑수열을 동반한 chloroquine 저항성 수입 열대열 말라리아를 Fansidar를 투여하여 치료가 된 1예를 경험하였기에 문헌고찰과 함께 보고하는 바이다. This previously healthy 26 year-old student was admitted to Cho Sun university hospital due to paroxysmal high fever, dizziness of 2 weeks duration and he also noted passage of dark brownish colored urine of 3 days duration. He had made journey to Africa for 2 months before admission. He had taken chloroquine 1 week before his jurney and continued this weekly throughout his stay. On admission, there was fever of 38.5℃ and numerous parasitemia of ring form of P. falciparum in the peripheral blood smear. On physical examination, he had jaundice and splenomgaly. On laboratory examination, he had jaundice and splenomegaly. On laboratory examination hemoglobin was 5.Og / dl, reticulocytecount was 11%, plasma hemoglobin was 7.5mg /dl and urine hemoglobin was 2.5mg /dl. He received Fansidar on 2nd day of admission. Five days later, his blood was completely clear of parasite and 7th day after admission, all symptoms were almost improved and then he was discharged.

IL-21-Expressing Mesenchymal Stem Cells Prevent Lethal B-Cell Lymphoma Through Efficient Delivery of IL-21, Which Redirects the Immune System to Target the Tumor

Kim, Nayoun,Nam, Young-Sun,Im, Keon-Il,Lim, Jung-Yeon,Lee, Eun-Sol,Jeon, Young-Woo,Cho, Seok-Goo Mary Ann Liebert 2015 STEM CELLS AND DEVELOPMENT Vol.24 No.23

원자력 발전소 핵연료 재장전을 위한 정지시 방사선준위 저감방법에 관한 연구

최형일,조영찬,오연옥 조선대학교 환경공해연구소 1999 環境公害硏究 Vol.15 No.-

During the shutdown of a pressurized water reactor, significant amounts of activated corrosion products were released. The recent recommendations by the Electric Power Research Institute for shutdown procedures aims to remove as much radioactivity as possible from the primary system. The Young-Gwang Nuclear Plant unit 4 performed a study to establish which conditions are reasonable to reduce the level of radioactivity in the primary system. The measurements include analysis of the reactor coolant, radioactivity in addition to boron concentration, pH, dissolved hydrogen and lithium concentration during shutdown. From these data estimates of the relation between Co-58 activity and other chemistry parameters (such as boron concentration, pH, dissolved hydrogen, lihthium concentration) have been made. The early removal of dissoled hydorgen and elevated boron concentration at acid reducing condition could affect the Co-58 dissociation rate. At acid oxidizing condition hydrogen peroxide could affect the dissolution of Co-58 which removed from the primary system. By using the purification ion exchanger remaining Co-58 could be removed to the level which primary manways of steam generator's can be open. The activity levels of each steam generator were lowered by 35% compared with that of last year. It indicates that low pH of the system chemistry through early removal of dissolved hydrogen and elevated boron concentration at high temperature accelerated the dissolution of Co-58.

원자력 발전소 핵연료 재장전을 위한 정지시 방사선준위 저감방법에 관한 연구

최형일,조영찬,오연옥 조선대학교 환경연구소 1999 環境硏究 Vol.15 No.1

During the shutdown of a pressurized water reactor, significant amounts of activated corrosion products were released. The recent recommendations by the Electric Power Research Institute for shutdown procedures aims to remove as much radioactivity as possible from the primary system. The Young-Gwang Nuclear Plant unit 4 performed a study to establish which conditions are reasonable to reduce the level of radioactivity in the primary system. The measurements include analysis of the reactor coolant, radioactivity in addition to boron concentration, pH, dissolved hydrogen and lithium concentration during shutdown. From these data estimates of the relation between Co-58 activity and other chemistry parameters (such as boron concentration, pH, dissolved hydrogen, lihthium concentration) have been made. The early removal of dissoled hydorgen and elevated boron concentration at acid reducing condition could affect the Co-58 dissociation rate. At acid oxidizing condition hydrogen peroxide could affect the dissolution of Co-58 which removed from the primary system. By using the purification ion exchanger remaining Co-58 could be removed to the level which primary manways of steam generator's can be open. The activity levels of each steam generator were lowered by 35% compared with that of last year. It indicates that low pH of the system chemistry through early removal of dissolved hydrogen and elevated boron concentration at high temperature accelerated the dissolution of Co-58.