간장 ( 肝腸 ) 및 담도 ( 膽道 ) : B형 활동성 간염 환자에서 단기 Prednisolone과 ARA - AMP 겸용 치료의 경과에 따른 면역 지표의 변화에 관한 연구

민영일(Young Il Min),장린(Rin Chang),김병호(Byung Ho Kim),장영운(Young Woon Chang),이정일(Joung Il Lee),황이숙(Yi Sook Hwang),김정원(Jeong Won Kim),김효종(Hyo Jong Kim) 대한소화기학회 1990 대한소화기학회지 Vol.22 No.3

N/A Withdrawal of corticosteroids in patients with chronic type B hepatitis is frequently associated with enhanced cellular immune response to hepatitis B virus. This immunolgic rebound generally results in a transient reduction in levels of HBV-DNA and DNA polymerase, and seldom results in clearance of HBeAg. There was a pilot study that the combination of a short course of prednisone followed by ARA-AMP was potentially synergistic. The object of this study was to determine the effect of short term prednisolone followed by ARA-AMP on the immune system in patients with chronic active ltepatitis-B. Patients were started 40 mg of prednisolone daily for 4 weeks. After prednisolone therapy was discontinued, patients received no medication for 2 weeks. ARA-AMP was then given for 4 weeks at a dose of 500 mg daily. Immune parameters such as T cell subsets, IL, production, NK cell activeity, and LAK cell activity were tested before and during treatement period. The resullts were as follows. 1) Basal IL2 production in CAH-B (71.3 unit/ml) was lower than that of normal control (p<0.025). Basal NK activity, T4/T8 ratio and LAK activity of CAH-B were similar to those of normal control. 2) After prednisolone treatment, IL2 production, NK cell activity and LAK cell activity were significantly lower than those of basal value. 3) After induction of immune rebound, IL, production increased to 84.8 unit/ml (basal 71.3 unit/ml,

Signal transducer and activator of transcription 3‐mediated CD133 up‐regulation contributes to promotion of hepatocellular carcinoma

Won, Cheolhee,Kim, Byung‐,Hak,Yi, Eun Hee,Choi, Kyung‐,Ju,Kim, Eun‐,Kyung,Jeong, Jong‐,Min,Lee, Jae‐,Ho,Jang, Ja‐,June,Yoon, Jung‐,Hwan,Jeong, Won‐,Il,P John Wiley and Sons Inc. 2015 Hepatology Vol.62 No.4

<P>Enhanced expression of the cancer stem cell (CSC) marker, CD133, is closely associated with a higher rate of tumor formation and poor prognosis in hepatocellular carcinoma (HCC) patients. Despite its clinical significance, the molecular mechanism underlying the deregulation of CD133 during tumor progression remains to be clarified. Here, we report on a novel mechanism by which interleukin‐6/signal transducer and activator of transcription 3 (IL‐6/STAT3) signaling up‐regulates expression of CD133 and promotes HCC progression. STAT3 activated by IL‐6 rapidly bound to CD133 promoter and increased protein levels of CD133 in HCC cells. Reversely, in hypoxic conditions, RNA interference silencing of STAT3 resulted in decrease of CD133 levels, even in the presence of IL‐6, with a concomitant decrease of hypoxia‐inducible factor 1 alpha (HIF‐1α) expression. Active STAT3 interacted with nuclear factor kappa B (NF‐κB) p65 subunit to positively regulate the transcription of HIF‐1α providing a mechanistic explanation on how those three oncogenes work together to increase the activity of CD133 in a hypoxic liver microenvironment. Activation of STAT3 and its consequent induction of HIF‐1α and CD133 expression were not observed in Toll‐like receptor 4/IL‐6 double‐knockout mice. Long‐term silencing of CD133 by a lentiviral‐based approach inhibited cancer cell‐cycle progression and suppressed <I>in vivo</I> tumorigenicity by down‐regulating expression of cytokinesis‐related genes, such as TACC1, ACF7, and CKAP5. We also found that sorafenib and STAT3 inhibitor nifuroxazide inhibit HCC xenograft formation by blocking activation of STAT3 and expression of CD133 and HIF‐1α proteins. <I>Conclusion</I>: IL‐6/STAT3 signaling induces expression of CD133 through functional cooperation with NF‐κB and HIF‐1α during liver carcinogenesis. Targeting STAT3‐mediated CD133 up‐regulation may represent a novel, effective treatment by eradicating the liver tumor microenvironment. (H<SMALL>EPATOLOGY</SMALL> 2015;62:1160‐1173)</P>

The Effect of Human Placental Extract on Rheumatoid Arthritis in an Animal Model

Jeong Dong Park,신희석,Sang-Il Lee,A Ram Kim,Jong Moon Park,Sang-Yeop Shin,Jun Hwa Shin,Seung Won Moon,Hyun Park,오민균 대한재활의학회 2012 Annals of Rehabilitation Medicine Vol.36 No.2

Objective To assess the effi cacy of human placental extract (HPE) in an animal model of rheumatoid arthritis (RA). Method We used (i) KRN C57BL/6 TCR transgenic x NOD mice (KBx/N) serum transfer arthritis and (ii) collageninduced arthritis (CIA) mice to evaluate the effi cacy of HPE (1 ul or 100 ul, intra-peritoneal, three times per week)on RA. Incidence, severity of arthritis, and hind-paw thickness were quantifi ed. Joint destruction was analyzed using modifi ed mammographic imaging. Histopathological analysis for infl ammation, cartilage, and osteoclasts was performed using Hematoxylin-eosin (H-E), safranin-O, and tartrate-resistant acidic phosphatase (TRAP). ELISAs were used for detection of various cytokines in serum and joint tissue. Results Th ere were no signifi cant diff erences in incidence of arthritis, clinical scores of arthritis, and hind-paw thickness between HPE-treated and vehicle-treated groups for up to 2 weeks in the KBx/N serum transfer arthritis model. Histopathological analysis also showed no diff erences 2 weeks after treatment. Levels of TNF-α, IL-1β, IL-6, IL-10, and RANKL in serum and joint tissues were similar in all groups. Furthermore, there were no diff erences in clinical, radiological, and histological parameters between HPE-treated and vehicle-treated group for 3 weeks in the CIA model. Conclusion Systemic treatment with HPE has no benefi cial eff ects on arthritis in animal models of RA. Th erefore,indiscreet use of HPE in RA should be forbidden.

Effect of Feed Selenium-lysine Supplementation on Milk Compositions and Serum Biochemical Indices in Saanen Dairy Goats

Tae-Il Kim,Dong-Hyun Lim,Tai-Young Hur,Seung-Min Ha,Hyun-Jong Kim,Seong-Min Park,Ji-Hoo Park,Sang-Bum Kim,Ji-Hwan Lee,Hyun-Joo Lim,Jeong-Sung Jung,Ha-Yeon Jeong,Jay Lee,Kwang-Seok Ki,Vijayakumar Mayak 경상대학교 농업생명과학연구원 2019 농업생명과학연구 Vol.53 No.4

An experiment was carried out to assess the effect of feed selenium-lysine (Se-Lys) supplementation on milk compositions and serum biochemical indices in Saanen dairy goats in Korea. A total of twelve 36 months old Saanen lactating dairy goats (47±6.21 kg) fed the similar dry matter intake twice a day at 2% of BW (DMI) (10.9% moisture of concentrate and 19% moisture of roughage), milk yield (2.5 kg/d) and parity (2) were randomly selected and subjected for the present study, divided into two groups with six goats in each group. The goats in the control group received rice hulls (10 g/ day) only, and did not receive Se-Lys; goats in the treatment group were fed 0.06 g of Se-Lys with 10 g of rice hulls every day before feeding roughage for six weeks. The milk sample was collected every week, and its compositions were analyzed. The results of the present study showed that there is no significantly increased milk production in Se-Lys treated group goats when compared with control group goats. But, Se-Lys treatment significantly increased the milk protein content (3.98±0.16%), fat (3.72±0.27%), lactose (4.07±0.14%), total solids (12.51±0.28%) and urea (14.42±1.45 mg/dl) content as compared to the control group goats (p<0.05). The somatic cell counts (207,740±28.81 cells/ml) were significantly lower in the Se-Lys treated group than in the control group (p<0.05). Also, the results of the current study showed that supplementation of Se-Lys were significantly decreased the blood biochemical indices of IL-6 (34.34±6.04 pg/ml), TNT-α (0.56±0.22 ng/ml), MDA (5.07±1.03 ng/ml), GPx-1 (9.07±5.17 ng/ml), sCD4 (2.64±1.02 ng/ml) and sCD8 (5.08±2.08 ng/ml) level when compared with without addition of Se-Lys group dairy goats (p<0.05). On the other hand, the selenoprotein P (1,580.18±127.62 ng/ml) level was significantly higher in Se-Lys supplemented group than in the control group (p<0.05). Based on the study results, it was concluded that feed Se-Lys supplementation may improve milk yield with positively improved protein, fat, lactose, total solids, urea content, and biochemical indices without negative effects on milk production traits.

Naringin Protects Ovalbumin-induced Asthma through the Down-regulation of MMP-9 Activity and GATA-3 Gene

Chang-Min Lee(이창민),Jeong Hyun Chang(장정현),In Duk Jung(정인덕),Young-Il Jeong(정영일),Noh Kyung Tae(노경태),Hee-ju Park(박희주),Jong-Suk Kim(김종석),Yong Kyoo Shin(신용규),Sung Nam Park(박성남),Yeong-Min Park(박영민) 한국생명과학회 2009 생명과학회지 Vol.19 No.6

Naringin은 레몬, 오렌지에서 발견되는 flavonoid계열에 속하는 물질로 여러 식물과 과일에 다량 함유되어 있다. 항암, 항산화 작용을 하는 것으로 알려져 있는 Naringin을 ovalbumin (OVA)으로 유도한 천식(asthma) 생쥐모델을 이용하여 치료효과를 알아 보았다. 기관지 폐포 세척액을 회수하여 백혈구의 수적 변화, 제2형 협조T세포(Th2 cell)가 생산하는 IL-4, IL-5의 생산에 미치는 영향과 폐조직에서 matrix metalloproteinase (MMP)-9 활성을 측정하였다. 또한, 최근에 Th1/Th2 전사인자로서 GATA-3가 밝혀졌는데 이번 실험에서 Naringin이 ovalbumin (OVA)으로 유도한 천식(asthma) 생쥐모델에서 Th1, Th2 싸이토카인과 유전자 발현을 조절할 수 있는가에 대하여 알아보았다 그 결과 기관지 폐포 세척액에서 OVA로 감작하여 천식을 유도한 실험군에서는 호산구의 현저한 증가, Th2 형 싸이토카인(IL-4, IL-5)의 증가가 관찰되었다. 그러나 Naringin을 투여한 그룹에서는 OVA의 감작에 의하여 증가한 각종 염증성 지표들이 감소하거나 정상화 되었다. 또한 OVA에 의하여 증가된 기도저항성이 Naringin 투여에 의하여 감소하였으며 폐조직의 염증성 소견도 뚜렷하게 감소되었다. 이와 같은 연구 결과는 Naringin이 천식의 치료에 유용하게 쓰일 수 있음을 시사해준다. The common word flavonoids is often used to classify a family of natural compounds, highly abundant in all higher plants, that have received significant therapeutic interest in recent years. Naringin is associated with a reduced risk of heart disease, neurodegenerative disease, cancer and other chronic diseases; however the molecular basis of this effect remains to be elucidated. Thus we attempted to elucidate the anti-allergic effect of Naringin in ovalbumin (OVA)-induced asthma model mice. The OVA-induced mice showed allergic reactions in the airways. These included an increase in the number of eosinophils in bronchoalveolar lavage (BAL) fluid, an increase in inflammatory cell infiltration into the lung around blood vessels and airways, airway luminal narrowing, and the development of airway hyper-responsiveness (AHR). The administration of Naringin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, this study may provide evidence that Naringin plays a critical role in the amelioration of the pathogenetic process of asthma in mice. These findings provide new insight into the immunopharmacological role of Naringin in terms of its effects on asthma in mice.

일반담배(Cigarette)와 금연 보조 담배(금연초, 허브담배, 쑥 담배)의 기관지 상피세포에서 IL-6유리 효과비교

김명찬 ( Myoung Chan Kim ),정재일 ( Je Il Jung ),정종훈 ( Jong Hoon Jung ),김학렬 ( Hak Ryul Kim ),양세훈 ( Sei Hoon Yang ),정은택 ( Eun Taik Jeong ),김휘정 ( Hui Jung Kim ) 대한결핵 및 호흡기학회 2005 Tuberculosis and Respiratory Diseases Vol.59 No.5

Comparison of Cytokine and Nitric Oxide Induction in Murine Macrophages between Whole Cell and Enzymatically Digested Bifidobacterium sp. Obtained from Monogastric Animals

Dong Woon Kim,Sung Back Cho,Hyun Jeong Lee,Wan Tae Chung,Kyoung Hoon Kim,Jong Hwangbo,In Sik Nam,Young Il Cho,양만표,Il Byung Chung 한국미생물학회 2007 The journal of microbiology Vol.45 No.4

The principal objective of this study was to compare the effects of whole and hydrolyzed cells(bifidobacteria) treated with gastrointestinal digestive enzymes on the activation of cloned macrophages. Seven different strains of Bifidobacterium obtained from swine, chickens, and rats, were digested with pepsin followed by pancreatin and the precipitate (insoluble fraction) and supernatant (soluble fraction) obtained via centrifugation. The RAW 264.7 murine macrophages were incubated with either whole cells, the precipitate, or supernatant at various concentrations. Pronounced increases in the levels of nitric oxide (NO), interleukin (IL)-1β, IL-6, IL-12, and tumor necrosis factor (TNF)-α were observed in the whole cells and precipitates, but these effects were less profound in the supernatants. The precipitates also evidenced a slight, but significant, inductive activity for NO and all tested cytokines, with the exception of TNF-α in the macrophage model as compared with the whole cells. By way of contrast, TNF-α production when cultured with whole cells (100 ng/ml) resulted in marked increases as compared with what was observed with the precipitates. The results of this study indicated, for the first time, that digested Bifidobacterium sp. can induce the production of NO and several cytokines in RAW 264.7 murine macrophage cells. In the current study, it was demonstrated that Bifidobacterium strains treated with digestive enzymes, as compared with whole cells, are capable of stimulating the induction of macrophage mediators, which reflects that they may be able to modulate the gastrointestinal immune functions of the host.

Pulmonary inflammation caused by silica dioxide nanoparticles in mice via TXNIP/NLRP3 signaling pathway

Je‑Oh Lim,Je‑Won Ko,Tae‑Yang Jung,Woong‑Il Kim,So‑Won Pak,In‑Sik Shin,Won‑Kee Yun,Hyoung‑Chin Kim,Jeong‑Doo Heo,Jong‑Choon Kim 대한독성 유전단백체 학회 2020 Molecular & cellular toxicology Vol.16 No.3

Background Silica dioxide nanoparticles (SiONPs) have been used for various medical applications, including therapeutics and imaging, and the use of SiONPs has increased gradually over the years. However, despite an increase in the use of SiONPs, not much is known about mechanism of action of SiONPs and their pulmonary toxicity. Objective The present study investigated the pulmonary toxicity of SiONPs and explored the underlying mechanism of action, primarily focusing on thioredoxin-interacting protein (TXNIP)/NOD-like receptor pyrin domain-containing 3 (NLRP3) in SiONPs-treated mice. We investigated the toxic effects of SiONPs in the lung of BALB/c mice administered 5, 10, and 20 mg/kg SiONPs for 3 days. Results Exposure to SiONPs markedly increased inflammatory cell counts, including those of neutrophils and macrophages, and levels of inflammatory mediators, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in a dose-dependent manner in the bronchoalveolar lavage fluid. Moreover, the inflammation was verified upon histopathological analysis. In addition, exposure to SiONPs increased the expression of TXNIP in a dose-dependent manner and, in turn, upregulated NLRP3 inflammasome proteins, which subsequently induced IL-1β production. Conclusion Collectively, exposure to SiONPs induced inflammation in the lungs of mice, which resulted in the activation of IL-1β production via the TXNIP-NLRP3 axis. Our results provide useful information on the pulmonary toxicity induced by SiONPs and provide insights into the underlying mechanism of action.

Comparison of Cytokine and Nitric Oxide Induction in Murine Macrophages between Whole Cell and Enzymatically Digested Bifidobacterium sp. Obtained from Monogastric Animals

Kim, Dong-Woon,Cho, Sung-Back,Lee, Hyun-Jeong,Chung, Wan-Tae,Kim, Kyoung-Hoon,HwangBo, Jong,Nam, In-Sik,Cho, Yong-Il,Yang, Mhan-Pyo,Chung, Il-Byung The Microbiological Society of Korea 2007 The journal of microbiology Vol.45 No.4

The principal objective of this study was to compare the effects of whole and hydrolyzed cells (bifidobacteria) treated with gastrointestinal digestive enzymes on the activation of cloned macrophages. Seven different strains of Bifidobacterium obtained from swine, chickens, and rats, were digested with pepsin followed by pancreatin and the precipitate (insoluble fraction) and supernatant (soluble fraction) obtained via centrifugation. The RAW 264.7 murine macrophages were incubated with either whole cells, the precipitate, or supernatant at various concentrations. Pronounced increases in the levels of nitric oxide (NO), interleukin $(IL)-1{\beta}$, IL-6, IL-12, and tumor necrosis factor $(TNF)-{\alpha}$ were observed in the whole cells and precipitates, but these effects were less profound in the supernatants. The precipitates also evidenced a slight, but significant, inductive activity for NO and all tested cytokines, with the exception of $(TNF)-{\alpha}$ in the macrophage model as compared with the whole cells. By way of contrast, $(TNF)-{\alpha}$ production when cultured with whole cells (100 ng/ml) resulted in marked increases as compared with what was observed with the precipitates. The results of this study indicated, for the first time, that digested Bifidobacterium sp. can induce the production of NO and several cytokines in RAW 264.7 murine macrophage cells. In the current study, it was demonstrated that Bifidobacterium strains treated with digestive enzymes, as compared with whole cells, are capable of stimulating the induction of macrophage mediators, which reflects that they may be able to modulate the gastrointestinal immune functions of the host.

백혈병 마우스 모델의 동종골수이식에서 활성화된 자연살해세포들의 보충이 이식편대백혈병효과와 이식편대숙주반응에 미치는 영향

엄현석,한치화,박수정,김소연,정낙균,정대철,진종률,최일봉,양형모,서영훈,송현근,최인표,민우성,김춘추 대한조혈모세포이식학회 2001 대한조혈모세포이식학회지 Vol.6 No.1

배경: 백혈병에서 동종골수이식 (allogeneic bone marrow transplantation)의 성공적 치료 효과를 얻기 위해서는 이식편대숙주반응 (graft-versus-host disease, GVHD) 발생의 극복과 재발의 방지가 중요한 과제이다. 골수를 역류원심성 세포분리 (counterflow centrifugal elutriation, CCE) 방법으로 분리하여 얻은 rotor off (R/O) 세포분획은 T 세포의 수는 적지만 조혈모세포들을 다량 포함하고 있어 동종골수이식에서 주조직적합복합체 (major histocompatibility complex, MHC) 차이를 극복할 수 있고, 이식편의 생착 성공과 GVHD 발생 예방에 효과적이다. 그러나 골수로부터 T 세포를 제거하면 백혈병세포를 공격하는 이식편대백혈병 (graft-versus-leukemia, GVL) 효과가 감소되기 때문에 백혈병 재발의 빈도가 높다. 자연살해세포 (natural killer cell, NK cell)의 보충 첨가는 동종골수이식 후 GVHD 발생을 줄이면서 충분한 GVL 효과를 얻을 수가 있다. 따라서 저자는 분리 후 IL-2로 활성화시킨 NK 세포들을 골수 R/O 세포분획과 함께 백혈병 마우스 모델에 동종이식함으로써 GVHD와 GVL에 미치는 효과를 관찰하였다. 방법: Balb/c (H-2^(d)) 마우스에서 유래된 A20 (murine B-lymphoma/leukemia cell line, H-2^(d)) 백혈병 세포를 이식 2 일 전에 Balb/c 마우스에 주입하고, 치사량의 전신 방사선을 조사한 직후에 Balb/c 또는 C57BL/6 (H-2^(b)) 마우스의 골수 R/O 세포분획을 꼬리정맥을 통하여 주입하였다. 이들은 모두 이식 후 6-8 주 이내에 사망하였다. 동종이식의 대조군 (n=9)에는 1 × 10^(7)의 R/O 세포분획만을 주입하였고, 실험군 (n=9)에는 C57BL/6 마우스의 비장세포들로부터 단클론항체들을 이용한 negative selection방법으로 분리한 후 IL-2로 활성화된 5 × 10^(5)의 NK 세포분획을 1 × 10^(7)의 R/O 세포분획과 함께 주입하였다. GVL 효과의 판정은 이식 후 14 일과 28 일 째 되는 날 마우스에서 골수, 비장, 간 등을 얻어 백혈병 세포들의 침윤을 조직학적으로 관찰하였으며, GVHD의 정도는 육안적 관찰법으로 평가하였다. 결과: R/O 세포분획만을 이식한 대조군의 골수, 비장, 그리고 간 조직에서는 A20 백혈병 세포의 침윤이 각각 89% (8/9), 78% (7/9)와 22% (2/9)에서 관찰되었고, R/O 세포분획과 NK 세포분획을 함께 이식한 실험군에서는 비장과 간을 제외한 골수에서만 89% (8/9)에서 A20 백혈병 세포의 침윤이 관찰되어 두 군 사이에 장기별 분포의 차이를 볼 수 있었다 (P= 0.0001). 한편 GVHD는 두 군 모두에서 경하게 나타나서 유의한 차이는 없었다. 또한 생착 부전으로 사망한 마우스는 없었다. 결론: CCE를 이용하여 T 세포를 제거한 동종골수이식에서 NK 세포의 보충은 GVHD의 악화는 일으키지 않으면서, 백혈병의 진행을 억제하는 GVL 효과를 얻을 수 있었다. Background: Allogeneic bone marrow transplantation (BMT) with T cell-depleted marrow accompanies engraftment failure and relapse of leukemia by a loss of the graft-versus-leukemia (GVL) effect frequently, while it can prevent GVHD. Supplement of NK cells could prevent GVHD and enhance GVL effect in several murine allogeneis BMT models Roter off (R/O) cell fraction obtained by counterflow centriation elutriatio (CCO) contains small number of T cells and many hematopoietic stem cells. The aim of this study was to determine the effect of R/O cell fraction supplemented with IL-2 activated NK cells on GVL and GVHD within the leukemic mouse BMT model. Methods: Inoculation of A20 (H-2d, murine B-lymphoma/leukemia, Balb/c origin) cells into Balb/c mice via the tail vein 2 days prior to lethal total body irradiation (TBI) and infusion of the Balb/c BM or C57BL/6 (H-2b) R/O fraction were performed. It resulted in 100% mortality within 6 to 8 weeks. The irradiated mice in the control group were injected with 1 × 107 R/O cell fraction alone (n=9) and in the experimental group mice were injected with 1 × 107 R/O cell fraction plus 5 × 105 negatively selected IL-2 activated NK cell fractions of the spleens via the tail vein (n=9). On day 14 and 28 after BMT, the bone marrows, spleens, and livers of mice were harvested for histopathologic analysis of the infiltrations of leukemic cells. We then evaluated the GVHD within the mice. Results: A histopathologic study of the recipients receiving R/O fraction alone showed infiltration of leukemic cells, 89% (8/9) in bone marrows, 78% (7/8) in spleens, and 22% (2/9) in livers. The experimental group of mice showed only the infiltration of leukemic cells 89% (8/9) in bone marrows, not in spleens and livers. There were the organ differences of the leukemic cells infiltrations between the two groups (P=0.0001). There were no obvious differences in the GVHD scores between these two groups, and severe GVHD was not observed. There was no engraftment failure among groups. Conclusion: Thus, our findings suggest that R/O cell fraction obtained by CCE and supplemented with NK cells can promote GVL effect without mediating clinically overt GVHD in allogeneic BMT of mouse leukemia.