• Title/Summary/Keyword: IL2RA

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Hominis Placenta suppress Calcium release, cyclooxygenase expression and PGE2 synthesis (자하거(紫河車)가 칼슘재흡수, cyclooxygenase의 발현, PGE2 생합성에 미치는 영향)

  • Jeong, Yeon-Ho;Kim, Ra-Young;Lee, Tae-Kyun;Kim, Dong-Il
    • The Journal of Korean Obstetrics and Gynecology
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    • v.18 no.1
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    • pp.55-63
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    • 2005
  • Purpose : 자하거(Hominis Placenta; HP)는 건강한 사람의 태반을 홍제(烘製)하여 건조한 것으로 한의학에서는 기혈(氣血)을 대보(大補)하고 신정(腎精)을 보익(補益)시켜 구병(久病)으로 인한 신체허약(身體虛弱)이나 혹은 체질허약(體質虛弱)과 혈기부족(氣血不足) 및 신허정휴(腎虛精虧) 등 등(證)을 치료(治療)하는데 단미(單味) 또는 복방(複方)에 배오(配伍)하여 쓰여왔다. 또한 자하거는 면역학적으로 골대사 활성이 있는 것으로 알려져 있어 본 연구에서는 자하거의 항골다공증 활성을 분자세포생물학적으로 검정하고자 하였다. Methods : Osteoblast cells에서 자하거가 COX-2 mRNA의 발현과 $PGE_2$ 생합성을 억제시키는지를 관찰하기 위해 먼저 TNF-${\alpha}$, IL-${\beta}$ 와 IL-6를 처리한 후 $PGE_2$의 생합성과 더불어 COX-2 mRNA의 발현을 확인하였다. 그 후 TGF-${\beta}$, 자하거(紫河車)와 이 둘의 조합인 자하거+TGF-${\beta}$가 COX-2 mRNA 발현과 $PGE_2$ 생합성을 저해시키는지 관찰하였다. 또한 자하거가 IL-1${\beta}$로 유발된 흰쥐의 과칼슘혈증을 감소시키는지를 확인하였다. Results : IL-6, IL-1${\beta}$와 TNF-${\alpha}$를 동시에 처리하면 이것을 단독으로 처리한 것과 비교해 볼 때 $PGE_2$의 생합성과 더불어 COX-2 mRNA의 수치가 상승작용을 일으키며 증가하였다. TGF-${\beta}$, 자하거와 이 둘의 조합인 자하거+TGF-${\beta}$은 COX-2 mRNA 발현, $PGE_2$ 생합성 및 골재흡수를 감소시켰다. 자하거(紫河車)는 IL-1${\beta}$, TNF-${\alpha}$와 IL-6 각각 또는 이들의 조합으로 인해 증가하는 COX-2 mRNA 발현과 $PGE_2$ 생성을 감소시키는 반면 COX-1 mRNA 발현에는 유의성 있는 영향을 미치지 않았다. 한편 자하거는 농도의존적으로 IL-1${\beta}$로 유발된 흰쥐의 과칼슘혈증을 감소시켰다. 이러한 결과는 흰쥐의 두개골 골아세포에서 $PGE_2$ 생산에 대한 IL-${\beta}$, TNF-${\alpha}$, IL-6의 상승작용이 COX-2의 유전자 발현 증가에 기인함을 보여주었다. Conclusions : 이러한 결과들로부터 자하거가 골대사과정중 골재흡수를 억제하는데 효과적임을 밝히게 되었으며, 자하거의 골다공증의 억제기전이 골재흡수관련 단백질들의 전사조절에 있음을 최초로 해명하게 되었다.

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Intra-articular Injection of $IL-1{\beta}$ Facilitated Formalin-induced Temporomandibular Joint Pain in Freely Moving Rats

  • Choi, Hyo-Soon;Jung, Sung-Chul;Choi, Byung-Ju;Ahn, Dong-Kuk
    • The Korean Journal of Physiology and Pharmacology
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    • v.9 no.1
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    • pp.23-27
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    • 2005
  • The present study was performed to investigate the effects of intra-articular injection of interleukin-1${\beta}$ (IL-1${\beta}$) on the formalin-induced temporomandibular joint (TMJ) pain. Under anesthesia, a 30-gauge needle was introduced into the right TMJ region for injection of formalin. Microinjection of 50 ${\mu}l$ of 5% formalin significantly produced noxious scratching behavioral response, and the scratching behavior lasted for 40 min. Although the responses produced by formalin injection were divided into two phases, the response of 1st phase did not significantly differ from the scratching behavior response in the saline-treated group. We examined the effects of intra-articular injection of IL-1${\beta}$ on the number of noxious behavioral responses produced by 50${\mu}l$ of 5% formalin injection. Intra-articular injection of 100 pg and 1 ng of IL-1${\beta}$ significantly increased the number of behavioral responses of the 2nd phase, while 10 pg of IL-1${\beta}$ did not change the formalin-induced behavioral responses. To investigate whether IL-1 receptor was involved in the intra-articular administration of IL-1${\beta}$-induced hyperalgesic response, IL-1 receptor antagonist (IL- ra, 50 ng) was administrated together with IL-1${\beta}$ injection. IL-1${\beta}$ receptor antagonist blocked IL-1${\beta}$- induced hyperalgesic response in the TMJ formalin test. These results suggest that intra-articular injection of IL-1${\beta}$ facilitated the transmission of nociceptive information in the TMJ area.

The Ability of Cervus Elaphus Sibiricus Herbal Acupuncture to Inhibit the Generation of Inflammatory Enzymes on Collagen-induced Arthritis Mice (녹용약침(鹿茸藥鍼)이 CIA 모델 생쥐의 염증인자 생성억제에 미치는 영향)

  • Hwang, Jong-Soon;Hwang, Ji-Hye;Lee, Hyun-Jin;Lee, Dong-Gun;Kang, Min-Joo;Back, Song-Ook;Cho, Hyun-Seok;Kim, Kyung-Ho;Kim, Kap-Sung
    • Journal of Acupuncture Research
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    • v.24 no.6
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    • pp.1-14
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    • 2007
  • Backgrounds : Rheumatoid Arthritis(RA) is known as the chronic inflammatory diseasethat induces persistent inflammation in the joint cavity. The destruction of cartilage occurs as the result of bones destoyed by pannus, several influential cytokines induced by the synovial capsulitis, varieties of proteinases, $O_2$ radicals, and the secondary degenerative changes of articular cartilage. The type 2 collagen-induced arthritis model is used in recent experimental research on rheumatoid arthritis. Cervus elaphus sibiricus (Nockyong) has the effect of relieving pain by nourishing the muscles, joints, and bones. It is also known to be efficacious in promoting and enhancing the immune system. The objective of this study was to investigate the effect of Cervus elaphus sibiricus herbal acupuncture to inhibit the generation of proinflammatory enzyme on type 2 collagen-induced arthritis. I investigated the inhibition of mRNA transcription of MIF(macrophage migration inhibitory factor), $TNF-{\alpha}$(Tumor necrosis $factor-{\alpha}$) and MMP-9 (matrix metalloproteinase-9) of Cervus elaphus sibiricus herbal acupuncture using an in vitro test. Also investigated was the inhibition of differentiation of Th 1 cells and activation of cytokines(MIF, $TNF-{\alpha}$, IL-6, MMP-9), which are known to cause initial RA ,and are also related to the morphology of the synovial membranes of the joint capsule, by an in vivo test, using CIA(collagen induced arthritis) model mice. Materials & methods : The laboratory animals used in this experiment were 4 week-old DBA female mice, weighing approximately 20 grams, and adjusted to the laboratory environment. The experiment was divided into the normal group(NOR)-no treated group, control group(CON)-CIA induced group, and sample group(SAM)-Cervus elaphus sibiricus herbal acupuncture treated group. RA was induced in the mice via injection of $50{\mu}{\ell}$ C II mixed CFA. The Cervus elaphus sibiricus herbal acupuncture solution was applied on $GB_{35}$(陽陵泉) for 26 days from the 3rd day of RA inducement. The concentration of the solution was determined via a MTT assay. To research the effect on the expression of MIF, $TNF-{\alpha}$ and MMP-9 mRNA, RT-PCR was performed on synovial membrane cells from the knee joint of CIA mice. C II induced RA knee joint's histo-chemical synovial membrane was observed using a specimen model via the Hematoxilin and Eosin dying technique. Results : The expression of mRNA of RA-related cytokines such as MIF, $TNF-{\alpha}$, and MMP-9 dosedependently decreased in the cell from the synovial membranes of the joint, which is treated with Cervus elaphus sibiricus herbal acupuncture solution. In mice treated with Cervus elaphus sibiricusherbal acupuncture, the damage of synovial membranes of the joint was lessened, and differentiation of Th 1 cells was suppressed. The activation of RA-related cytokines such as MIF was suppressed, and the generation of $TNF-{\alpha}$ and MMP-9 showed a statistically significant decreas. Conclusions : It is speculated that Cervus elaphus sibiricus herbal acupuncture has the therapeutic effect of palliating the damage of the tissue impaired by RA by inhibition of the initial RA progression and by regulating excessive differentiation of Th 1 cell as it suppresses the generation of RA-related cytokines during the highest stage of RA by acting on pro-inflammatory enzymes.

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Suppressive Effect of CYTG on Collagen Induced Arthritis(CIA) in DBA1/J Mice (CYTG 처방이 콜라겐 유발 관절염 모델에 미치는 효과)

  • Choi, Sung-Wook;Kim, Yong-Chan;Kim, Kyoung-Shin;Kim, Byoung-Soo;Lim, Jong-Soon;Kang, Jung-Soo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.1
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    • pp.62-69
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    • 2007
  • To evaluate effect of CYTG on inhibiting the occurrence of arthritis, we performed the experiments including production of inflammatory cytokine and immunoglobulin in collagen arthritis model. The results were obtained as fellows. CYTG group showed inhibitory effect on arthritis incidence than control group for four weeks. Arthritis index of CYTG group reduced compared with control group. In CYTG group, production of cytokines which show suppressive effect on inflammation(IL-2, COX-2) was increased and which promotes inflammation(IL-10) was decreases in spleen. In CYTG group, production of immunoglobulin (IgG-RF) was reduced compared with control, and rate of CD3+CD69+T cell is lower in lymph node and CD4+CD25+ T cell is higher in lymph node and spleen. And synovial infiltration in the knee were observed in the controls (PBS-treated mice), whereas CYTG-treated mice exhibited significantly reduced histologic evidence of destruction and inflammation. So, the histopathological scoring average of CYTG group was 2.5 compared with control group(CIA mice) 4.5. It was thought that our data express high effect via immune system specially through the controling the inflammatory cytokines and immunoglobulins. CYTG could be usefully applied for the prevention and treatment of RA, and also is expected to be clinically helpful on the treatment of RA through modification.

Studies on the Effect of Corilagin Isolated from Euphorbia helioscopia on Collagen-Induced Arthritis (II);CytokinesAnalysis of Collagen II Induced Arthritis Mice Model (택칠에서 분리한 Corilagin이 Collagen 유발 관절염에 미치는 영향 (II);Corilagin을 투여한 류마티스 관절염 유발 생쥐의 사이토카인 분석)

  • Shin, Sam-Kee;Chang, Jun-Pok;Doh, Eun-Soo
    • Korean Journal of Plant Resources
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    • v.21 no.4
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    • pp.336-340
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    • 2008
  • Corilagin (CRN) isolated from Euphorbia helioscopia as rheumatoid arthritis drug. CRN was medicated to the abdominal cavity of collagen induced arthritis (CIA) mice that was an animal model for rheumatoid arthritis and its effects on incidence and arthritis index were studied. The results were as folllows; It was exhibited that medicating corilagin inhibited the infiltration of activated T lymphocytes into an inflammatory joint. The production of IgG and IgM that were RF (rheumatoid factor) and inflammatory cytokine, IL-6 and $TNF-{\alpha}$were reduced. After measuring $IFN-{\gamma}$and IL-4, it was found that it was shifted into Th2 immune response as increasing in IL-4. After liver function test, studies on liver poisoning of AST/ALT should be continued.

The Effect of Ramulus Cinnamomum Aqua - acupuncture on The Cellular Immune Responses to LPS Induced Arthritis in Mice (계지약침자극(桂枝藥鍼刺戟)이 mouse의 LPS유발(誘發) 관절염(關節炎) 중 세포성면역반응(細胞性免疫反應)에 미치는 영향(影響))

  • Cho, Yoo-Haeng;Kim, Kap-Sung;Lee, Seung-Deok
    • Journal of Acupuncture Research
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    • v.18 no.1
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    • pp.100-112
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    • 2001
  • Objective : The purpose of this study is to investigate the immunological effect of Ramulus Cinnamomum aqua-acupuncture on the cellular immune response in mice with LPS induced arthritis. Methods : All the BALB/C mice used in this study were bred and maintaned in our pathogen-free mouse colony and were 6wk of age at the start of the experiment. The experimental model of arthritis was induced by injeciton of 300${\mu}g$/kg LPS in mice knee joint. Ramulus Cinnamomum aqua-acupuncture was injected into Yangnungchon(Gb34) of mice 2daily for 14days. Immunohistochemical analysis was carried out to assess CD4+, CD8+, CD11b, IL-$1{\beta}$, IL-2R and CD106 expression in common iliac lymph nodes and synovial menbrane after stimulation with Ramulus Cinnamomum. Electron microscopy was carried out to assess change of synovial membrane. Ramulus Cinnamomum aqua-acupuncture stimulation group was compared to control group and non stimutated with aqua-acupuncture. Resutts : At day 14 post arthritis onset, Immunohistological studies using monoclonal antibodies showed that Ramulus Cinnamomum aqua-acupuncture goup had decreased expression of CD4+, CD8+, CD11b, IL-$1{\beta}$, IL-2R and CD106 at common illiac lymph nodes and synovial membrane compared with control group. Conclusions : Ramulus Cinnamomum aqua-acupuncture stimulation inhibited the development of cellular immunity to LPS-induced arthritis in mice. Thus, aqua-acupuncture stimulation may have preventive effects on autoimmune inflammatory joint diseases. The effects of AA on immune function and disease activity in patients with RA warrant further investigation.

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Serum Cytokine Levels are related to Nesfatin-1/NUCB2 Expression in the Implantation Sites of Spontaneous Abortion Model of CBA/j×DBA/2 Mice

  • Chung, Yiwa;Kim, Heejeong;Seon, Sojeong;Yang, Hyunwon
    • Development and Reproduction
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    • v.21 no.1
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    • pp.35-46
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    • 2017
  • The process of spontaneous abortion involves a complex mechanism with various cytokines, growth factors, and hormones during the pregnancy. However, the mechanism underlying spontaneous abortion by pro- and anti-inflammatory cytokines in the serum during the pregnancy is not fully understood. Therefore, the purpose of this study was to examine the relationship between the serum levels of pro- and anti-inflammatory cytokines and spontaneous abortion using the $CBA/j{\times}DBA/2$ mouse model. Serum levels of pro-inflammatory cytokines, such as $IFN-{\gamma}$, $IL-1{\alpha}$ and $TNF-{\alpha}$ were not increased in abortion model mice, but anti-inflammatory cytokines, such as IL-4, IL-13 and IL-1ra were decreased compared to normal pregnant mice. In addition, serum levels of chemokine, such as SDF-1, G-CSF, M-CSF, IL-16, KC and MCP-1 were decreased in abortion model mice compared to normal pregnant mice. However, the expression levels of nesfatin-1/NUCB2 mRNA and protein in the uteri of implantation sites were significantly higher in abortion model mice than normal pregnant mice. These results suggest that uterine nesfatin-1/NUCB2 expression may be down-regulated by inflammatory cytokines and chemokines in the serum of pregnant mice. Moreover, this study suggests the possibility that nesfatin-1/NUCB2 expressed in the implantation sites may be associated with the maintenance of pregnancy.

Determinants of Reduced Bone Mass in Postmenopausal Women with Rheumatoid Arthritis (폐경 후 류마티스 관절염 여성의 골량감소 판별요인)

  • Lee, Eun-Nam
    • The Korean Journal of Rehabilitation Nursing
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    • v.2 no.2
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    • pp.193-205
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    • 1999
  • This study was carried out to identify the important risk factors for reduced bone mass of postmenopausal RA patients and to develop discriminant function which can classify postmenopausal RA patients with either reduced or normal bone mass. Through the literature review, individual characteristics such as age, body weight, height, age of menarche, duration of menopause, gravity, parity, and breast feeding period and factors of life style such as milk consumption exercise habit, alcohol intake, cigarette smoking, coffee consumpt ion , disease activity, corticosteroid therapy were identified as influencing factors of reduced bone mass in RA patients Sixty eight postmenopausal women with rheumatoid arthritis aged between 42 and 76 were selected among those who checked bone mineral density in lumbar spine and femur from october, 1998 to Apr il, 1999 at Dong-a university hospital in Pusan. Assessment of disease activity, duration of disease and corticosteroid therapy were made by the same rheumatologist and included Ritchie articular index, erythrocyte sedimentation rate, and C-reactive protein on measuring bone mineral density. Cumulative steroid dosage was calculated from the daily dosage multiplied by t h e number of days received. The information of other risk factor including health assessment score, individual characteristics and life style factors were collected by questionnaire. Bone mineral density(BMD) was measured using DXA at lumbar spine and femoral Ward's triangle. Discriminant function(regression equation) was developed for estimating the likelihood of the presence or absence of reduced bone mass. The results are as follows: Among the subjects, thirteen(19.1%) exhibited osteoporosis in lumbar spine and twenty four(35.3%) exhibited osteoporosis in femoral Ward's triangle. For lumbar spine, the variables significant were age, body weight, health assessment score, while for femoral Ward's triangle, age, body weight, duration of disease. But disease activity and corticosteroid therapy were not signigicant to distinguish reduced bone mass from normal bone mass. When the discriminant function was evaluated by comparing the observed out come with predicted out come, the discriminant function correctly classified 85.4% of patients with reduce bone mass and 63.0% of patients with normal bone mass in the lumbar spine and 100% of patients with reduced bone mass and 9.1% of patients with normal bone mass in the femoral Ward's triangle. In summary, we found that osteoporosis in postmenopausal women with RA is more evident at the femur than the lumbar spine. Also the important discriminant factors of reduced bone mass postmenopausal women with RA were age, body weight , duration of disease and health disability. In nursing situation, the efforts to improve of functional capacity of postmenopausal women with rheumatoid arthritis should be considered to prevent osteoporosis and fractures. Also we recommend those postmenopausal women with RA who are classified as a group of the reduced bone mass in the discriminant function should examine the bone mineral density to further examine the usefulness of this discriminant function.

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Effects of All-trans retinoic acid on the cholangiocarcinogenesis in Hamsters infected with Clonorchis sinensis (All-trans retinoic acid 투여가 간흡충 감염 햄스터의 담관암 발생에 미치는 영향)

  • Kim, Hak-yeop;Seo, Il-bok
    • Korean Journal of Veterinary Research
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    • v.36 no.1
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    • pp.151-159
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    • 1996
  • This study was carried out to evaluate the effects of all-trans retinoic acid(RA) on the development of cholangiocarcinoma in hamsters. Eighty six female Syrian golden hamsters were divided into four groups. Group I was for the induction of the cholangiocarcinoma, which was infected orally with C sinensis and given dimethylnitrosamine(DMN, 15ppm) in drinking water for 4 weeks. Group II was for evaluating the effect of all-trans RA treatment on the cholangiocarcinogenesis, which was treated the same as group I and orally given RA(1mg/kg, 5 times per week) for 15 weeks. Group III was given only RA hr 15 weeks. Control group IV was given only soybean oil which was solvent for RA treatment. More than 5 heads of hamsters in each group were sacrificed at 4, 7, 11 and 15 weeks after the begining of the experiment. The livers were examined grossly, histopathologically, and immunohistochemically. The results obtained were as follows : 1. Death of animals started from the 11 weeks after the begining of the experiment. One of the total 22 animals(5%) and 7 of the total 24 animals(29%) died in group I and group II, respectively. 2. Proliferation of oval cell was peaked at 11 weeks in group I and at 7 weeks in group II, and decreased gradually after those periods of the time. 3. Cholangiocarcinomas were found in 1 of 6 animals(17%) at 11 weeks and in 4 of 6 animals(67%) at 15 weeks in group I, respectively. But in group II, the cholangiocarcinomas occured in 1 of 5 animals(20%) at 7 weeks, in 7 of 12 animals(58%) at 11 weeks and in 2 of the rest animals(100%) at 15 weeks, respectively. 4. Expression of $\alpha$-fetoprotein(AFP) of the oval cells in the group II showed the same degree of positive reaction at that of group I at 4 weeks. But AFP postive oval cells decreased gradually and AFP negative oval cells(ductlike oval cells) increased gradually. 5. Expression of cytokeratin of the oval cells in group II was shown slightly at 4 weeks and the degree of expression increased moderately from the 7 weeks. But the expression of the oval cells in group I was shown slightly after the 7 weeks. These results suggested that all-trans RA promoted the occurrence and the rate of cholangiocarcinoma by inducing differentiation of small cells and oval cells in the liver of hamsters infected with C sinensis and treated with DMN.

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