Effects of Moxibustion to Zusanli(ST36) on Alteration of Natural Killer Cell Activity in Rats

Choi, Gi Soon,Han, Jae Bok,Park, Joon Ha,Oh, Sang Deog,Lee, Gi Seog,Bae, Hyun Su,Jung, Sung Ki,Cho, Young Wuk,Ahn, Hyun Jong,Min, Byung Il WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2004 東西醫學硏究所 論文集 Vol.2004 No.-

Moxibustion is one of the major healing techniques in Oriental medicine. It has been widely used in many diseases such as rheumatoid arthritis, Hashimoto disease, breech presentation, etc. However, till now, effects of moxibustion on natural killer (NK) cell activity and relations between sympathetic nerve system (SNS) and the immune alteration induced by moxibustion wert not well studied. This study was designed to evaluate effects of moxibustion on NK cell activity and the Intervention of SNS in the alteration of NK cell activity induced by moxibustion. Splenic NK cell cytotoxicity was measured in a standard 4-hour ^(51)Cr release assay. We measured the NK cell cytotoxicity after moxibustion stimulation for 1, 3, 5 and 7 days, and also measured the NK cell cytotoxicity after 3 and 7 days burn stimulation with similar temperature. Interleukin (IL)-2, -4 and interferon (INF)-γ in serum were measured by rat IL-2, -4 and INF-γ ELISA test kit. To evaluate the effects of sympathectomy on alteration of NK cell cytotoxicity, 6-hydroxydopamine (6-OHDA: 50 mg/kg) was used. We showed that NK cell activity of moxibustion stimulation group incrcased at the 3rd day, and declined at the 7th day in comparison with that of the control group. In thc moxibustion stimulation group, NK cell activity was significantly higher than the sham group at the 3rd day. On the contrary, in the burn stimulation group, NK cell activity was significantly higher than that of the sham groups at 3rd and 7th days. INF-γ level after 3 days in the moxibustion stimulation group was significantly higher than that of the sham group. IL-2 Ievel among groups were not different. IL-4 was not detected in serum with this method. Sympathectomy abolished the NK cell activity alteration induced by moxibustion. The results suggest that moxibustion modulates NK cell activity, along with INF-γ, and SNS is mediating these effects.

麻醉前處置劑 Flunt (Ro 5-4200)과 Meperidine HCI의 比較的 硏究

金庸樂,咸秉文,崔重立,郭一龍 한국의 현대의학사 1974 한국의 현대의학 Vol.7 No.1

Effects of Aralia cordata Thunb. on Proteoglycan Release, Type II Collagen Degradation and Matrix Metalloproteinase Activity in Rabbit Articular Cartilage Explants

Baek, Yong-Hyeon,Seo, Byung-Kwan,Lee, Jae-Dong,Huh, Jeong-Eun,Yang, Ha-Ru,Cho, Eun-Mi,Choi, Do-Young,Kim, Deog-Yoon,Cho, Yoon-Je,Kim, Kang-Il,Park, Dong-Suk The Korean Acupuncture Moxibustion Medicine Societ 2005 대한침구의학회지 Vol.33 No.4

Background & Objective: Articular cartilage is a potential target for drugs designed to inhibit the activity of matrix metalloproteinases (MMPs) to stop or slow the destruction of the proteoglycan and collagen in the cartilage extracellular matrix. The purpose of this study was to investigate the effects of Aralia cordata Thunb. in inhibiting the release of glycosaminoglycan (GAG), the degradation of collagen, and MMP activity in rabbit articular cartilage explants. Methods : The cartilage-protective effects of Aralia cordata Thunb. were evaluated by using glycosaminoglycan degradation assay, collagen degradation assay, colorimetric analysis of MMP activity, measurement of lactate dehydrogenase activity and histological analysis in rabbit cartilage explants culture. Results : Interleukin-la (IL-1a) rapidly induced GAG, but collagen was much less readily released from cartilage explants. Aralia cordata Thunb. significantly inhibited GAG and collagen release in a concentration-dependent manner. Aralia cordata Thunb. dose-dependently inhibited MMP-3 and MMP-13 expression and activities from IL-1a-treated cartilage explants cultures when tested at concentrations ranging from 0.02 to 0.2 mg/ml. Aralia cordata Thunb. had no harmful effect on chondrocytes viability or cartilage morphology in cartilage explants. Histological analysis indicated that Aralia cordata Thunb. reduced the degradation of the cartilage matrix compared with that of IL -1a-treated cartilage explants.

Effects of Aralia cordata Thunb. on Proteoglycan Release, Type II Collagen Degradation and Matrix Metalloproteinase Activity in Rabbit Articular Cartilage Explants

Baek, Yong-Hyeon,Seo, Byung-Kwan,Lee, Jae-Dong,Huh, Jeong-Eun,Yang, Ha-Ru,Cho, Eun-Mi,Choi, Do-Young,Kim, Deog-Yoon,Cho, Yoon-Je,Kim, Kang-Il,Park, Dong-Suk The Korean AcupunctureMoxibustion Medicine Society 2005 대한침구의학회지 Vol.22 No.2

Background & Objective: Articular cartilage is a potential target for drugs designed to inhibit the activity of matrix metalloproteinases (MMPs) to stop or slow the destruction of the proteoglycan and collagen in the cartilage extracellular matrix. The purpose of this study was to investigate the effects of Aralia cordata Thunb. in inhibiting the release of glycosaminoglycan (GAG), the degradation of collagen, and MMP activity in rabbit articular cartilage explants. Methods : The cartilage-protective effects of Aralia cordata Thunb. were evaluated by using glycosaminoglycan degradation assay, collagen degradation assay, colorimetric analysis of MMP activity, measurement of lactate dehydrogenase activity and histological analysis in rabbit cartilage explants culture. Results : Interleukin-la (IL-1a) rapidly induced GAG, but collagen was much less readily released from cartilage explants. Aralia cordata Thunb. significantly inhibited GAG and collagen release in a concentration-dependent manner. Aralia cordata Thunb. dose-dependently inhibited MMP-3 and MMP-13 expression and activities from IL-1a-treated cartilage explants cultures when tested at concentrations ranging from 0.02 to 0.2 mg/ml. Aralia cordata Thunb. had no harmful effect on chondrocytes viability or cartilage morphology in cartilage explants. Histological analysis indicated that Aralia cordata Thunb. reduced the degradation of the cartilage matrix compared with that of IL -1a-treated cartilage explants.

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>

Effect of Cytokines and bFGF on the Osteoclast Differentiation Induced by 1α,25-(OH)<SUB>2</SUB>D<SUB>3</SUB> in Primary Murine Bone Marrow Cultures

Han-Jung Chae,Jang-Sook Kang,Byung-Gwan Bang,Seoung-Bum Cho,Jo-IL Han,Joo-Young Choi,Hyung-Min Kim,Soo-Wan Chae,Hyung Ryong Kim 대한생리학회-대한약리학회 1999 The Korean Journal of Physiology & Pharmacology Vol.3 No.6

<P> Bone is a complex tissue in which resorption and formation continue throughout life. The bone tissue contains various types of cells, of which the bone forming osteoblasts and bone resorbing osteoclasts are mainly responsible for bone remodeling. Periodontal disease represents example of abnormal bone remodeling. Osteoclasts are multinucleated cells present only in bone. It is believed that osteoclast progenitors are hematopoietic origin, and they are recruited from hematopoietic tissues such as bone marrow and circulating blood to bone. Cells present in the osteoclast microenvironment include marrow stromal cells, osteoblasts, macrophages, T-lymphocytes, and marrow cells. These cells produce cytokines that can affect osteoclast formation. In vitro model systems using bone marrow cultures have demonstrated that IL-1β, IL-3, TNF-α, bFGF can stimulate the formation of osteoclasts. In contrast, IL-4 inhibits osteoclast formation. Knowledge of cytokines and bFGF that affect osteoclast formation and their capacity to modulate the bone-resorbing process should provide critical insights into normal calcium homeostasis and disorders of bone turnover such as periodontal disease, osteoporosis and Paget s disease.

주조직적합항원이 불일치하는 마우스 동종 조혈모세포이식에서 IL-2로 유도된 CD4+CD25+ T세포를 이용한 이식편대숙주병의 억제

현재호,정대철,정낙균,박수정,민우성,김태규,최병옥,김원일,한치화,김학기,Hyun, Jae Ho,Jeong, Dae Chul,Chung, Nak Gyun,Park, Soo Jeong,Min, Woo Sung,Kim, Tai Gyu,Choi, Byung Ock,Kim, Won Il,Han, Chi Wha,Kim, Hack Ki 대한면역학회 2003 Immune Network Vol.3 No.4

Background: In kidney transplantation, donor specific transfusion may induce tolerance as a result of some immune regulatory cells against the graft. In organ transplantation, the immune state arises from a relationship between the immunocompromised graft and the immunocompetent host. However, a reverse immunological situation exists between the graft and the host in hematopoietic stem cell transplantation (HSCT). In addition, early IL-2 injections after an allogeneic murine HSCT have been shown to prevent lethal graft versus host disease (GVHD) due to CD4+ cells. We investigated the induction of the regulatory CD4+CD25+ cells after a transfusion of irradiated recipient cells with IL-2 into a donor. Methods: The splenocytes (SP) were obtained from 6 week-old BALB/c mice ($H-2^d$) and irradiated as a single cell suspension. The donor mice (C3H/He, $H-2^k$) received $5{\times}10^6$ irradiated SP, and 5,000 IU IL-2 injected intraperitoneally on the day prior to HSCT. The CD4+CD25+ cell populations in SP treated C3H/He were analyzed. In order to determine the in vivo effect of CD4+CD25+ cells, the lethally irradiated BALB/c were transplanted with $1{\times}10^7$ donor BM and $5{\times}10^6$ CD4+CD25+ cells. The other recipient mice received either $1{\times}10^7$ donor BM with $5{\times}10^6$ CD4+ CD25- cells or the untreated SP. The survival and GVHD was assessed daily by a clinical scoring system. Results: In the MLR assay, BALB/c SP was used as a stimulator with C3H/He SP, as a responder, with or without treatment. The inhibition of proliferation was $30.0{\pm}13%$ compared to the control. In addition, the MLR with either the CD4+CD25+ or CD4+CD25- cells, which were isolated by MidiMacs, from the C3H/He SP treated with the recipient SP and IL-2 was evaluated. The donor SP treated with the recipient cells and IL-2 contained more CD4+CD25+ cells ($5.4{\pm}1.5%$) than the untreated mice SP ($1.4{\pm}0.3%$)(P<0.01). There was a profound inhibition in the CD4+CD25+ cells ($61.1{\pm}6.1%$), but a marked proliferation in the CD4+CD25- cells ($129.8{\pm}65.2%$). Mice in the CD4+CD25+ group showed low GVHD scores and a slow progression from the post-HSCT day 4 to day 9, but those in the control and CD4+CD25- groups had a high score and rapid progression (P<0.001). The probability of survival was 83.3% in the CD4+CD25+ group until post-HSC day 35 and all mice in the control and CD4+CD25- groups died on post-HSCT day 8 or 9 (P=0.0105). Conclusion: Donor graft engineering with irradiated recipient SP and IL-2 (recipient specific transfusion) can induce abundant regulatory CD4+CD25+ cells to prevent GVHD.

Activation of NKT Cells in an Anti-PD-1–Resistant Tumor Model Enhances Antitumor Immunity by Reinvigorating Exhausted CD8 T Cells

Bae, Eun-Ah,Seo, Hyungseok,Kim, Byung-Seok,Choi, Jeongwon,Jeon, Insu,Shin, Kwang-Soo,Koh, Choong-Hyun,Song, Boyeong,Kim, Il-Kyu,Min, Byung Soh,Han, Yoon Dae,Shin, Sang Joon,Kang, Chang-Yuil American Association for Cancer Research 2018 Cancer Research Vol.78 No.18

<P>These findings provide mechanistic insights into the application of NKT cell stimulation as a potent adjuvant for immunotherapy against advanced cancer.</P><P>PD-1–based cancer immunotherapy is a successful example of immune checkpoint blockade that provides long-term durable therapeutic effects in patients with cancer across a wide spectrum of cancer types. Accumulating evidence suggests that anti-PD-1 therapy enhances antitumor immunity by reversing the function of exhausted T cells in the tumor environment. However, the responsiveness rate of patients with cancer to anti-PD-1 therapy remains low, providing an urgent need for optimization and improvement. In this study, we designed an anti-PD-1–resistant mouse tumor model and showed that unresponsiveness to anti-PD-1 is associated with a gradual increase in CD8 T-cell exhaustion. We also found that invariant natural killer T cell stimulation by the synthetic ligand α-galactosylceramide (αGC) can enhance the antitumor effect in anti-PD-1–resistant tumors by restoring the effector function of tumor antigen–specific exhausted CD8 T cells. IL2 and IL12 were among the cytokines produced by αGC stimulation critical for reinvigorating exhausted CD8 T cells in tumor-bearing mice and patients with cancer. Furthermore, we observed a synergistic increase in the antitumor effect between αGC-loaded antigen-presenting cells and PD-1 blockade in a therapeutic murine tumor model. Our study suggests NKT cell stimulation as a promising therapeutic strategy for the treatment of patients with anti-PD-1–resistant cancer.</P><P><B>Significance:</B> These findings provide mechanistic insights into the application of NKT cell stimulation as a potent adjuvant for immunotherapy against advanced cancer. <I>Cancer Res; 78(18); 5315–26. ©2018 AACR</I>.</P>

<i>In vivo</i> genotoxicity evaluation of lung cells from Fischer 344 rats following 28 days of inhalation exposure to MWCNTs, plus 28 days and 90 days post-exposure

Kim, Jin Sik,Sung, Jae Hyuck,Choi, Byung Gil,Ryu, Hyeon Yeol,Song, Kyung Seuk,Shin, Jae Hoon,Lee, Jong Seong,Hwang, Joo Hwan,Lee, Ji Hyun,Lee, Gun Ho,Jeon, Kisoo,Ahn, Kang Ho,Yu, Il Je Informa Healthcare 2014 INHALATION TOXICOLOGY Vol. No.

<P>Despite their useful physico-chemical properties, carbon nanotubes (CNTs) continue to cause concern over occupational and human health due to their structural similarity to asbestos. Thus, to evaluate the toxic and genotoxic effect of multi-wall carbon nanotubes (MWCNTs) on lung cells <I>in vivo</I>, eight-week-old rats were divided into four groups (each group = 25 animals), a fresh air control (0 mg/m<SUP>3</SUP>), low (0.17 mg/m<SUP>3</SUP>), middle (0.49 mg/m<SUP>3</SUP>), and high (0.96 mg/m<SUP>3</SUP>) dose group, and exposed to MWCNTs <I>via</I> nose-only inhalation 6 h per day, 5 days per week for 28 days. The count median length and geometric standard deviation for the MWCNTs determined by TEM were 330.18 and 1.72 nm, respectively, and the MWCNT diameters ranged from 10 to 15 nm. Lung cells were isolated from five male and five female rats in each group on day 0, day 28 (only from males) and day 90 following the 28-day exposure. The total number of animals used was 15 male and 10 female rats for each concentration group. To determine the genotoxicity of the MWCNTs, a single cell gel electrophoresis assay (Comet assay) was conducted on the rat lung cells. As a result of the exposure, the olive tail moments were found to be significantly higher (<I>p</I> < 0.05) in the male and female rats from all the exposed groups when compared with the fresh air control. In addition, the high-dose exposed male and middle and high-dose exposed female rats retained DNA damage, even 90 days post-exposure (<I>p</I> < 0.05). To investigate the mode of genotoxicity, the intracellular reactive oxygen species (ROS) levels and inflammatory cytokine levels (TNF-α, TGF- β, IL-1, IL-2, IL-4, IL-5, IL-10, IL-12 and IFN-γ) were also measured. For the male rats, the H<SUB>2</SUB>O<SUB>2</SUB> levels were significantly higher in the middle (0 days post-exposure) and high- (0 days and 28 days post-exposure) dose groups (<I>p</I> < 0.05). Conversely, the female rats showed no changes in the H<SUB>2</SUB>O<SUB>2</SUB> levels. The inflammatory cytokine levels in the bronchoalveolar lavage (BAL) fluid did not show any statistically significant difference. Interestingly, the short-length MWCNTs deposited in the lung cells were persistent at 90 days post-exposure. Thus, exposing lung cells to MWCNTs with a short tube length may induce genotoxicity.</P>

사람 성상세포종 세포주에서 사이토카인에 의한 Fas 및 FasL mRNA의 발현 조절

김옥준,임정희,최철희,최인홍,이병인,최일생 대한신경과학회 1999 대한신경과학회지 Vol.17 No.1